Ligand-based magnetic extraction and safety assessment of zinc oxide nanoparticles in food products.

Zinc oxide (ZnO) is a zinc supplement widely used in health products and is approved by the FDA as Generally Regarded as Safe (GRAS). However, concerns have arisen regarding the potential health effects of nanoscale ZnO, as its reactivity differs from that of its bulk form. This has led to the need for an efficient method to extract ZnO from food products without altering its physicochemical properties, where conventional methods have proven to be inadequate. This study introduces an innovative approach using starch magnetic particles (SMPs) functionalized with a 12-amino acid peptide modified with five lysines (ZBP), that has specific affinity to ZnO. ZBP@SMPs effectively and rapidly extract intact ZnO from food products, achieving recovery efficiencies ranging from 60% to 90%, all while maintaining its morphology and crystallinity. The diameter of ZnO particles recovered from six commercial food products ranged from 25 to 500 nm, with 33% falling below 100 nm, highlighting the need for a size-dependent toxicity study. However, cytotoxicity assessment on human intestinal Caco-2 cells shows all ZnO samples affects cell proliferation and membrane integrity in a dose-dependent manner due to partial dissolution. This study contributes to understanding the safety of ZnO-containing food products and highlights potential health implications associated with their consumption.

Vitamin D3 decreases myoblast fusion during the growth and increases myogenic gene expression during the differentiation phase in muscle satellite cells from Korean native beef cattle.

The process of myogenesis, which involves the growth and differentiation of muscle cells, is a crucial determinant of meat yield and quality in beef cattle. Essential nutrients, such as vitamins D and A, play vital roles in the development and maintenance of various tissues, including muscle. However, limited knowledge exists regarding the specific effects of vitamins A and D in bovine muscle. Therefore, the aim of this study was to investigate the impact of vitamins A and D treatment on myogenic fusion and differentiation in bovine satellite cells (BSC). BSC were isolated from Korean native beef cattle, specifically from four female cows approximately 30 mo old. These individual cows were used as biological replicates (n = 3 or 4), and we examined the effects of varying concentrations of vitamins A (All-trans retinoic acid; 100 nM) and D (1,25-dihydroxy-vitamin D3; 1 nM, 10 nM, and 100 nM), both individually and in combination, on myoblast fusion and myogenic differentiation during the growth phase (48 h) or differentiation phase (6 d). The results were statistically analyzed using GLM procedure of SAS with Tukey's test and t-tests or one-way ANOVA where appropriate. The findings revealed that vitamin A enhanced the myoblast fusion index, while vitamin D treatment decreased the myoblast fusion index during the growth phase. Furthermore, vitamin A treatment during the differentiation phase promoted terminal differentiation by regulating the expression of myogenic regulatory factors (Myf5, MyoD, MyoG, and Myf6) and inducing myotube hypertrophy compared to the control satellite cells (P < 0.01). In contrast, vitamin D treatment during the differentiation phase enhanced myogenic differentiation by increasing the mRNA expression of MyoG and Myf6 (P < 0.01). Moreover, the combined treatment of vitamins A and D during the growth phase increased myoblast fusion and further promoted myogenic differentiation and hypertrophy of myotubes during the differentiation phase (P < 0.01). These results suggest that vitamin A and D supplementation may have differential effects on muscle development in Korean native beef cattle during the feeding process.

The study investigated the effects of vitamins A and D on the growth and differentiation phases of bovine satellite cells and found that both vitamins have a positive impact on muscle development. Vitamin A promoted myoblast fusion during the growth phase, leading to increased myotube formation, while vitamin D suppressed myoblast fusion during this phase. However, during the differentiation phase, both vitamins enhanced terminal differentiation and hypertrophy. Vitamin A promoted the activation of satellite cells, while vitamin D promoted the expression of genes that enhance myogenesis. The combination treatment of vitamins A and D during the growth phase complemented each other to increase myogenic cell fusion, and during differentiation, promoted terminal differentiation and hypertrophy. These findings suggest that supplementing cattle feed with both vitamins A and D has the potential to enhance muscle development, which would be advantageous for the meat industry.

Panax ginseng C.A. meyer alleviates benign prostatic hyperplasia while preventing finasteride-induced side effects.

Panax ginseng C.A. Meyer, a widely used traditional medicine in East Asia, shows many beneficial effects on immune function, male erectile dysfunction, cancer, excessive oxidants, and aging issues. However, its effect on benign prostatic hyperplasia (BPH) and its potential in the treatment of side effects related to finasteride (Fi), an FDA-approved drug for BPH, are less known. This study aimed to verify the therapeutic effects of a water extract of P. ginseng (PGWE) on BPH in testosterone propionate (TP)-induced BPH rats and TP-treated RWPE-1 human epithelial cells, and the inhibitory potential on the Fi-induced side effects is also explored. In the TP-induced BPH rat model, PGWE alleviated the pathological markers of BPH such as weight and epithelial thickness of the prostate, and the serum level of dihydrotestosterone. PGWE downregulated androgen-related BPH factors such as 5α-reductase 2 and androgen receptor. PGWE also showed prostatic cell apoptosis accompanied by increased expression of Bax and decreased expression of Bcl-xL and cleaved-caspase 3, respectively, in addition to increasing mitochondrial dynamics in both in vivo and in vitro BPH models. Notably, reduced sperm count, one of the serious side effects of Fi, in the epididymis of BPH rats was recovered with PGWE treatment, suggesting less toxicity to sperm development by PGWE. PGWE also protected against Fi-induced sperm loss when PGWE was administered in combination with Fi without compromising the therapeutic effects of Fi on BPH. Based on these findings, we propose that PGWE could be an alternative therapeutic agent for BPH.

Therapeutic role of Glycyrrhiza Uralensis fisher on benign prostatic hyperplasia through 5 alpha reductase regulation and apoptosis.

BACKGROUND: Benign prostatic hyperplasia (BPH) is an age-related disease in adult men. There are two pharmacological treatments for BPH. However, these synthetic materials have various risks, many studies are being conducted to develop new drugs from natural sources. PURPOSE: In this study, we proposed a beneficial effect of Glycyrrhiza uralensis Fischer on the development and progression of BPH, focusing on the androgen receptor (AR) and 5α-reductase 2 (5AR2) signaling axis. METHODS: To explain the therapeutic efficacy of a water extract of G. uralensis (GUWE) for BPH, we used testosterone propionate (TP)-induced BPH rat models and TP-treated RWPE-1 human prostate epithelial cells. RESULTS: In the TP-induced BPH rat models, GUWE reduced the enlarged prostate weight, prostate index, prostate epithelial thickness, and serum DHT levels. In addition, the protein levels of AR and 5AR2 in prostate tissues were significantly decreased by GUWE treatment. Furthermore, GUWE induced apoptosis signaling through an increase of Bcl-2 associated X protein (Bax), caspase 3, and Poly (ADP-ribose) polymerase (PARP) and a decrease of B-cell lymphoma-extra-large (Bcl-xL) in prostate tissues of TP-induced BPH rats. These findings were also confirmed in TP-treated RWPE-1 cells. Fi treatment markedly decreased the sperm count in the epididymis of BPH rats, but GUWE treatment did not affect the sperm count, suggesting less toxicity. CONCLUSION: These findings suggested that GUWE reduces the development of BPH by inhibiting AR-5AR2 and activating the apoptosis signaling pathway. Furthermore, unlike finasteride, GUWE did not affect sperm count. Therefore, we suggest that GUWE has a potential as a safer alternative option for BPH treatment.

Anti-obesity Effects of Dark Tea Extracts by Down-regulation of C/EBPα and PPARγ.

BACKGROUND/AIM: Dark tea, made by fermentation of tea leaves using microorganisms, is well known for its antiobesity effect; however, studies to identify this effect have not been sufficiently conducted. Herein, the anti-obesity effects of post-fermented dark tea were studied in high-fat diet mouse. MATERIALS AND METHODS: Obesity was induced through a high-fat diet in C57BL/6 mice, and then dark tea extract powder (DTP) was orally administered daily for 12 weeks to evaluate the body and organ weights. Changes in the biochemical markers of obesity were evaluated to study the mechanism of the anti-obesity effects of DTP. RESULTS: When DTP was administered to obesity mice, the weight and food intake reduced, blood aspartate aminotransferase (AST), alanine aminotransferase (ALT), triglyceride (TG), low-density lipoprotein-cholesterol (LDL-C) decreased, whereas high-density lipoprotein cholesterol (HDL-C) increased. Histopathology showed that steatosis and inflammation scores were reduced within the liver and adipocyte sizes were reduced within epididymal adipocyte. In addition, a significant decrease in blood insulin and hepatic TG and a significant increase in blood adiponectin were also confirmed. The results of western blot and qPCR in week 12, showed a significant decrease in the mRNA and protein levels of C/EBPα, and the mRNA levels of PPARγ in the liver. CONCLUSION: Dark tea extracts are thought to have an anti-obesity effect by reducing the levels of the main transcription factors that promote adipocyte differentiation, such as C/EBPα, and PPARγ. Therefore, diet products using dark tea extracts could be developed.

Ellagic acid improves benign prostate hyperplasia by regulating androgen signaling and STAT3.

Benign prostate hyperplasia (BPH) is an age-related disease in men characterized by the growth of prostate cells and hyperproliferation of prostate tissue. This condition is closely related to chronic inflammation. In this study, we highlight the therapeutic efficacy of ellagic acid (EA) for BPH by focusing on the AR signaling axis and STAT3. To investigate the effect of EA on BPH, we used EA, a phytochemical abundant in fruits and vegetables, to treat testosterone propionate (TP)-induced BPH rats and RWPE-1 human prostate epithelial cells. The EA treatment reduced prostate weight, prostate epithelial thickness, and serum DHT levels in the TP-induced BPH rat model. In addition, EA improved testicular injury by increasing antioxidant enzymes in testis of the BPH rats. EA reduced the protein levels of AR, 5AR2, and PSA. It also induced apoptosis by regulating Bax, Bcl_xL, cytochrome c, caspase 9, and caspase 3 with increasing mitochondrial dynamics. Furthermore, EA reduced the expression of IL-6, TNF-α, and NF-κB, as well as phosphorylation of STAT3 and IκBα. These findings were also confirmed in TP-treated RWPE-1 cells. Overall, our data provide evidence of the role of EA in improving BPH through inhibition of AR and the STAT3 pathway.

Comparison of the Efficacy and Safety of Atorvastatin 40 mg/ω-3 Fatty Acids 4 g Fixed-dose Combination and Atorvastatin 40 mg Monotherapy in Hypertriglyceridemic Patients who Poorly Respond to Atorvastatin 40 mg Monotherapy: An 8-week, Multicenter, Randomized, Double-blind Phase III Study.

PURPOSE: Residual cardiovascular risk in patients with hypertriglyceridemia, despite optimal low-density lipoprotein cholesterol levels being achieved with intensive statin treatment, is a global health issue. The purpose of this study was to investigate the efficacy and tolerability of treatment with a combination of high-dose atorvastatin/Ω-3 fatty acid compared to atorvastatin + placebo in patients with hypertriglyceridemia who did not respond to statin treatment. METHODS: In this multicenter, randomized, double-blind, placebo-controlled study, patients who had residual hypertriglyceridemia after a 4-week run-in period of atorvastatin treatment were randomly assigned to receive UI-018 (fixed-dose combination atorvastatin/Ω-3 fatty acid 40 mg/4 g) or atorvastatin 40 mg + placebo (control). The primary efficacy end points were the percentage change from baseline in non-high density lipoprotein cholesterol (non-HDL-C) level at the end of treatment and the adverse events recorded during treatment. A secondary end point was the percentage change from baseline in triglyceride level. FINDINGS: After 8 weeks of treatment, the percentage changes from baseline in non-HDL-C (-4.4% vs +0.6%; p = 0.02) and triglycerides (-18.5% vs +0.9%; p < 0.01) were significantly greater in the UI-018 group (n = 101) than in the control group (n = 99). These changes were present in subgroups of advanced age (≥65 years), status (body mass index ≥25 kg/m2), or without diabetes. The prevalences of adverse events did not differ between the 2 treatment groups. IMPLICATIONS: In patients with residual hypertriglyceridemia despite receiving statin treatment, a combination of high-dose atorvastatin/Ω-3 fatty acid was associated with a greater reduction of triglyceride and non-HDL-C compared with atorvastatin + placebo, without significant adverse events.

Fruit of Hovenia dulcis Thunb. Induces Nonshivering Thermogenesis through Mitochondrial Biogenesis and Activation by SIRT1 in High-Fat Diet-Fed Obese Mice and Primary Cultured Brown Adipocytes.

Brown adipocytes, which contain abundant mitochondria, use stored energy as fuel during a process named nonshivering thermogenesis. Thus, the pharmacological activation of thermogenesis in brown adipose tissue (BAT) has become a promising target for treating obesity. We investigated the effect of fruit of Hovenial dulcis Thunb. (FHD), a frequently used herbal treatment for liver diseases, on thermogenesis and its mechanism using primary cultured brown adipocytes and BAT of high-fat-diet (HFD)-induced obese mice. Thermogenesis-related factors including UCP1 and PGC1α increased with FHD treatment. FHD also increased mitochondrial biogenesis and activation factors such as nuclear respiratory factor (NRF)1 and oxidative phosphorylation (OXPHOS) complex. Furthermore, FHD increased the intercellular nicotinamide adenine dinucleotide (NAD+) level and sirtuin 1 (SIRT1) activity, which may be responsible for the activation of the thermogenic reaction. Overall, our results suggest that FHD can be a novel option for obesity treatment due to its thermogenic action through mitochondrial biogenesis and activation.

Synthesis of polypyrrole nanorods via sacrificial removal of aluminum oxide nanopore template: A study on cell viability, electrical stimulation and neuronal differentiation of PC12 cells.

Synthesis of nanomaterials having uniform shape and size is a challenging task. Properties exhibited by such substrates would be compatible and homogeneous compared to the average properties displayed by those substrates with heterogeneous size. Herein, we report the synthesis of polypyrrole nanorods (PPy-NRs) of almost uniform size via oxidative chemical polymerization of pyrrole within anodized aluminum oxide nanopores followed by sacrificial removal of the template. Field emission scanning electron microscopy (FE-SEM), fourier transformed infra-red (FT-IR) spectra, X-ray diffraction (XRD), and ultra-violet-visible-near infra-red (UV-Vis-NIR) spectra of the substrate were used to analyze the physicochemical properties of as-synthesized PPy-NRs. PPy-NRs treated MC3T3-E1 and PC12 cells exhibited good biocompatibility in CCK-8 and live/dead assays. The assay showed more cell viability on PC12 cell lines. Electrical stimulation through PPy-NRs treated PC12 cells accelerated neuronal differentiation compared to those without electrical stimulation during in vitro cell culture.

Identification and metabolite profiling of alkaloids in aerial parts of Papaver rhoeas by liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry.

Papaver plants can produce diverse bioactive alkaloids. Papaver rhoeas Linnaeus (common poppy or corn poppy) is an annual flowering medicinal plant used for treating cough, sleep disorder, and as a sedative, pain reliever, and food. It contains various powerful alkaloids like rhoeadine, benzylisoquinoline, and proaporphine. To investigate and identify alkaloids in the aerial parts of P. rhoeas, samples were collected at different growth stages and analyzed using liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry. A liquid chromatography with mass spectrometry method was developed for the identification and metabolite profiling of alkaloids for P. rhoeas by comparing with Papaver somniferum. Eighteen alkaloids involved in benzylisoquinoline alkaloid biosynthesis were used to optimize the liquid chromatography gradient and mass spectrometry conditions. Fifty-five alkaloids, including protoberberine, benzylisoquinoline, aporphine, benzophenanthridine, and rhoeadine-type alkaloids, were identified authentically or tentatively by liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry in samples taken during various growth stages. Rhoeadine alkaloids were observed only in P. rhoeas samples, and codeine and morphine were tentatively identified in P. somniferum. The liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry method can be a powerful tool for the identification of diverse metabolites in the genus Papaver. These results may help understand the biosynthesis of alkaloids in P. rhoeas and evaluate the quality of this plant for possible medicinal applications.

Antioxidant effects of Cirsium setidens extract on oxidative stress in human mesenchymal stem cells.

Human mesenchymal stem cells (MSCs) may be used in cell-based therapy to promote neovascularization for the treatment of ischemic diseases. However, high levels of reactive oxygen species (ROS) derived from the pathophysiological ischemic environment induce senescence and apoptosis of MSCs, resulting in reduced functionality and defective neovascularization. Therefore, the present study aimed to determine the protective effects of Cirsium setidens, a natural product, on oxidative stress­induced apoptosis in MSCs. The present study investigated for the change of ROS levels in MSCs using ROS assays. In addition, cell viability determined by MTT and TUNEL assays. Western blot analysis was performed to investigate the change of apoptosis­associated proteins in MSCs. Treatment of MSCs with hydrogen peroxide (H2O2; 200 µM) significantly increased intracellular ROS levels and cell death; however, pretreatment with C. setidens (100 µg/ml) suppressed H2O2­induced ROS generation and increased the survival of MSCs. H2O2­induced ROS production increased the levels of phosphorylated­p38 mitogen activated protein kinase, c­Jun N­terminal kinase, ataxia telangiectasia mutated and p53; these increases were inhibited by pretreatment with C. setidens. In addition, C. setidens inhibited ROS­induced apoptosis of MSCs by increasing the expression levels of the anti­apoptotic protein B­cell lymphoma 2 (BCL­2), and decreasing the expression levels of the proapoptotic protein BCL­2­associated X protein. These findings indicated that pretreatment of MSCs with C. setidens may prevent ROS­induced oxidative injury by regulating the oxidative stress­associated signaling pathway, and suppressing the apoptosis­associated signal pathway. Therefore, C. setidens may be developed as a beneficial broad­spectrum agent for enhancing the effectiveness of MSC transplantation in the treatment of ischemic diseases.

Anti-diabetic and anti-obesitic effects of aqueous extracts of Yangkyuksanhwa-tang and its two major compositions on db/db mice.

Type 2 diabetes mellitus (T2DM) is a metabolic syndrome that results from target-tissue resistance to insulin. Obesity is the condition of excess body fat accumulation. T2DM and obesity are both associated with hypertension, hyperlipidemia, and abdominal obesity. In Korean medicine, Yangkyuksanhwa-tang (YKSHT) has been prescribed for patients with T2DM. Oral glucose tolerance tests (OGTT), multiplex assays and hemoglobin A1C (HbA1C) assessments were performed to determine the anti-diabetic effects of YKSHT and two major compositions of YKSHT, Lonicera japonica Thunb. (LJT) and Rehmannia glutinosa (RG) on db/db mice, a rodent model for T2DM. To study the anti-obesitic effects of LJT, RG or YKSHT, blood profiling including the triglycerides (TGs) and the total, LDL and HDL cholesterol levels were measured. In addition, body index measures such as the liver, retroperitoneal and epididymal fat tissues were collected and weighed. Mice treated with RG or YKSHT showed reduced blood glucose levels after stimulating the plasma GLP-1 levels. The multiplex assay results support the weight-controlling effects of the LJT, RG and YKSHT treatments, showing reducing levels of ghrelin and the induction of peptide YY (PYY) secretion. The YKSHT treatment reduced plasma TG levels and increased HDL cholesterol levels. The weights of the liver, retroperitoneal and epididymal fat tissues were reduced after the YKSHT treatment. Hence, we suggest that YKSHT can be utilized for the prevention and treatment of T2DM and obesity simultaneously.

Cell cloning-on-the-spot by using an attachable silicone cylinder.

Cell cloning is a laboratory routine to isolate and keep particular properties of cultured cells. Transfected or other genetically modified cells can be selected by the traditional microbiological cloning. In addition, common laboratory cell lines are prone to genotypic drift during their continual culture, so that supplementary cloning steps are often required to maintain correct lineage phenotypes. Here, we designed a silicone-made attachable cloning cylinder, which facilitated an easy and bona fide cloning of interested cells. This silicone cylinder was easy to make, showed competent stickiness to laboratory plastics including culture dishes, and hence enabled secure isolation and culture for days of selected single cells, especially, on the spots of preceding cell-plating dishes under microscopic examination of visible cellular phenotypes. We tested the silicone cylinder in the monoclonal subcloning from a heterogeneous population of a breast cancer cell line, MDA-MB-231, and readily established independent MDA-MB-231 subclones showing different sublineage phenotypes.

Antihyperglycemic and Antiobesity Effects of JAL2 on db/db Mice.

Lonicera japonica Thunb. (LJT) and Rehmannia glutinosa Libosch. (RGL) have been used traditionally as a herbal medicine in Korean medicine. Using LC/Q-TOF was performed to profile the two herbal medicines and the mixture of LJR and RGL (JAL2, ratio 1 : 1). We performed oral glucose tolerance test (OGTT) and plasma GLP-1 and insulin secretion by multiplex assays to investigate antidiabetic effects of LJT, RGL, and JAL2 in db/db mice, the mice model of type 2 diabetes mellitus (T2DM). Also, the antiobesity-related factors such as plasma peptide YY (PYY), triglyceride, total cholesterol, HDL, LDL, and weight of liver, epididymal, and retroperitoneal fat tissue were investigated. Through the multiplex assay, it was found that JAL2 treatment more efficiently attenuated high levels of blood glucose by stimulating GLP-1 secretion and reduced LDL concentration and weight of liver and retroperitoneal fat tissue compared to LJT or RGL treated separately. These results suggest that the JAL2 has antidiabetes and antiobesity effects in T2DM mice model.

Paeonia lactiflora Enhances the Adhesion of Trophoblast to the Endometrium via Induction of Leukemia Inhibitory Factor Expression.

In the present study, we investigated the role of Paeonia lactiflora Pall. extract on embryo implantation in vitro and in vivo. A polysaccharides depleted-water extract of P. lactiflora (PL-PP) increased LIF expression in human endometrial Ishikawa cells at non-cytotoxic doses. PL-PP significantly increased the adhesion of the human trophectoderm-derived JAr spheroids to endometrial Ishikawa cells. PL-PP-induced LIF expression was decreased in the presence of a p38 kinase inhibitor SB203580 and an MEK/ERK inhibitor U0126. Furthermore, endometrial LIF knockdown by shRNA reduced the expression of integrins ß3 and ß5 and adhesion of JAr spheroids to Ishikawa cells. In vivo administration of PL-PP restored the implantation of mouse blastocysts in a mifepristone-induced implantation failure mice model. Our results demonstrate that PL-PP increases LIF expression via the p38 and MEK/ERK pathways and favors trophoblast adhesion to endometrial cells.

Fucoidan protects mesenchymal stem cells against oxidative stress and enhances vascular regeneration in a murine hindlimb ischemia model.

BACKGROUND: Mesenchymal stem cells (MSCs) have the potential to differentiate into multiple cell lineages. Given this potential for tissue regeneration, MSC-based therapeutic applications have been considered in recent years. However, ischemia-induced apoptosis has been reported to be one of the main causes of MSC death following transplantation. The primary objective of this study was to determine whether a natural antioxidant, fucoidan, could protect MSCs from ischemia-induced apoptosis in vitro and in vivo. Furthermore, we investigated the mechanism of action of fucoidan's anti-ischemic effect in MSCs. METHODS AND RESULT: Pre-treatment with fucoidan (10 µg/mL) suppressed the increase in H2O2-induced reactive oxygen species (ROS) levels and drastically reduced apoptotic cell death in MSCs. Fucoidan inhibited the activation of the pro-apoptotic proteins p38-mitogen-activated protein kinase (MAPK), Jun N-terminal kinase (JNK), and caspase-3, and augmented the expression of the anti-apoptosis protein cellular inhibitor of apoptosis (cIAP). Moreover, fucoidan significantly increased manganese superoxide dismutase (MnSOD) expression and decreased cellular ROS levels via the Akt pathway, resulting in enhanced cell survival. In a murine hindlimb ischemia model, transplanted fucoidan-treated MSCs showed significantly enhanced cell survival and proliferation in ischemic tissues. Functional recovery and limb salvage also remarkably improved in mice injected with fucoidan-stimulated MSCs compared with mice injected with non-stimulated MSCs. CONCLUSION: Taken together, these results show that fucoidan protects MSCs from ischemia-induced cell death by modulation of apoptosis-associated proteins and cellular ROS levels through regulation of the MnSOD and Akt pathways, suggesting that fucoidan could be powerful therapeutic adjuvant for MSC-based therapy in ischemic diseases.

Korean Red Ginseng Extract Enhances the Anticancer Effects of Imatinib Mesylate Through Abrogation p38 and STAT5 Activation in KBM-5 Cells.

Although imatinib mesylate (IM) in the treatment of chronic myelogenous leukemia (CML) remains the best example of successful targeted therapy, majority of patients with CML suffer its toxicity profile and develop chemoresistance to existing therapeutic agents. Thus, there is a need to develop novel alternative therapies for the treatment of CML. Here, we investigated whether Korean red ginseng extract (KRGE) could suppress the proliferation and induce chemosensitization in human CML cells. Also, we used a human phospho-antibody array containing 46 antibodies against signaling molecules to examine a subset of phosphorylation events after treatment. Korean red ginseng extract broadly suppressed the proliferation of five different cell lines, but KRGE was found to be the most potent inducer of apoptosis against KBM-5 cells. It also abrogated the expression of Bcl-2 (B-cell lymphoma 2), Bcl-xL (B-cell lymphoma-extra large), survivin, inhibitors of apoptosis protein 1/2, COX-2 (Cyclooxygenase-2), cyclin D1, matrix metalloproteinase-9, and VEGF (Vascular endothelial growth factor), as well as upregulated the expression of pro-apoptotic gene products. Interestingly, KRGE also enhanced the cytotoxic and apoptotic effect of IM in KBM-5 cells. The combination treatment of KRGE and IM caused pronounced suppression of p38 and signal transducer and activator of transcription 5 phosphorylation and induced phosphorylation of p53 compared with the individual treatment. Our results demonstrate that KRGE can enhance the anticancer activity of IM and may have a substantial potential in the treatment of CML.

Morusin induces cell death through inactivating STAT3 signaling in prostate cancer cells.

STAT3 has been recognized as an efficacious drug target for prostate cancer because of its constitutive activation in this fatal disease. We recently identified the root bark of Morus alba Linn. as a potential STAT3 inhibitor among 33 phytomedicines traditionally used in Korea. Morusin, an active compound isolated from the root bark of Morus alba, has shown anti-oxidant and anti-inflammatory effects. In the present study, we examined whether morusin has a potential as an anti-cancer agent in prostate cancer. We found that morusin suppressed viability of prostate cancer cells, but little effect in normal human prostate epithelial cells. Morusin also reduced STAT3 activity by inhibiting its phosphorylation, nuclear accumulation, and DNA binding activity. In addition, morusin down-regulated expression of STAT3 target genes encoding Bcl-xL, Bcl-2, Survivin, c-Myc and Cyclin D1, which are involved in regulation of apoptosis and cell cycle. Furthermore, morusin induced apoptosis in human prostate cancer cells by reducing STAT3 activity. Taken together, these results suggest that morusin could be a potentially therapeutic agent for prostate cancer by reducing STAT3 activity and inducing apoptosis.

Ginseng gintonin activates the human cardiac delayed rectifier K+ channel: involvement of Ca2+/calmodulin binding sites.

Gintonin, a novel, ginseng-derived G protein-coupled lysophosphatidic acid (LPA) receptor ligand, elicits [Ca(2+)]i transients in neuronal and non-neuronal cells via pertussis toxin-sensitive and pertussis toxin-insensitive G proteins. The slowly activating delayed rectifier K(+) (I(Ks)) channel is a cardiac K(+) channel composed of KCNQ1 and KCNE1 subunits. The C terminus of the KCNQ1 channel protein has two calmodulin-binding sites that are involved in regulating I(Ks) channels. In this study, we investigated the molecular mechanisms of gintonin-mediated activation of human I(Ks) channel activity by expressing human I(Ks) channels in Xenopus oocytes. We found that gintonin enhances IKs channel currents in concentration- and voltage-dependent manners. The EC50 for the I(Ks) channel was 0.05 ± 0.01 µg/ml. Gintonin-mediated activation of the I(Ks) channels was blocked by an LPA1/3 receptor antagonist, an active phospholipase C inhibitor, an IP3 receptor antagonist, and the calcium chelator BAPTA. Gintonin-mediated activation of both the I(Ks) channel was also blocked by the calmodulin (CaM) blocker calmidazolium. Mutations in the KCNQ1 [Ca(2+)]i/CaM-binding IQ motif sites (S373P, W392R, or R539W)blocked the action of gintonin on I(Ks) channel. However, gintonin had no effect on hERG K(+) channel activity. These results show that gintonin-mediated enhancement of I(Ks) channel currents is achieved through binding of the [Ca(2+)]i/CaM complex to the C terminus of KCNQ1 subunit.

Reversible dilated cardiomyopathy caused by idiopathic hypoparathyroidism.

Dilated cardiomyopathy (DCM) is usually an idiopathic disease with a poor prognosis. Hypocalcemia is a rare and reversible cause of DCM. Here, we report a 50-year-old female with DCM, induced by idiopathic hypoparathyroidism, that improved after treatment with calcium.