Stimuli-Responsive Drug Delivery of Doxorubicin Using Magnetic Nanoparticle Conjugated Poly(ethylene glycol)-g-Chitosan Copolymer.

Stimuli-responsive nanoparticles are regarded as an ideal candidate for anticancer drug targeting. We synthesized glutathione (GSH) and magnetic-sensitive nanocomposites for a dual-targeting strategy. To achieve this goal, methoxy poly (ethylene glycol) (MePEG) was grafted to water-soluble chitosan (abbreviated as ChitoPEG). Then doxorubicin (DOX) was conjugated to the backbone of chitosan via disulfide linkage. Iron oxide (IO) magnetic nanoparticles were also conjugated to the backbone of chitosan to provide magnetic sensitivity. In morphological observation, images from a transmission electron microscope (TEM) showed that IO nanoparticles were embedded in the ChitoPEG/DOX/IO nanocomposites. In a drug release study, GSH addition accelerated DOX release rate from nanocomposites, indicating that nanocomposites have redox-responsiveness. Furthermore, external magnetic stimulus concentrated nanocomposites in the magnetic field and then provided efficient internalization of nanocomposites into cancer cells in cell culture experiments. In an animal study with CT26 cell-bearing mice, nanocomposites showed superior magnetic sensitivity and then preferentially targeted tumor tissues in the field of external magnetic stimulus. Nanocomposites composed of ChitoPEG/DOX/IO nanoparticle conjugates have excellent anticancer drug targeting properties.

Erratum: Editorial Retraction: Optimization of Jirisan Mountain Cudrania Tricuspidata Leaf Substance Extraction Across Solvents and Temperatures.

[This corrects the article on p. 48 in vol. 21, PMID: 30151304.].

Shoulder Pain Treated by Manual Acupuncture and Pharmacopuncture Following Origin/Insertion Technique of Applied Kinesiology: A Case Series of Two Patients.

The aim of this study was to report on the improvement of shoulder pain resulting from disorders of the rotator cuff such as impingement syndrome and adhesive capsulitis, by manual acupuncture (MA) and pharmacopuncture (PA) following origin/insertion technique (OIT) of applied kinesiology (AK). Two patients were treated with MA and PA after OIT on shoulder muscles. The Numerical Rating Scale and the assessment of the Japanese Orthopedic Association scores were used to assess the pain, and ultrasound images were taken to compare treatment outcome. This study showed that MA and PA following OIT may be an effective treatment for impingement syndrome and adhesive capsulitis.

Editorial Retraction: A Review on the Role of Irisin in Insulin Resistance and Type 2 Diabetes Mellitus.

[This retracts the article on p. 235 in vol. 20, PMID: 30151293.].

Activation of the Nrf2/HO-1 signaling pathway contributes to the protective effects of baicalein against oxidative stress-induced DNA damage and apoptosis in HEI193 Schwann cells.

Baicalein, a flavonoid extracted from the roots of Scutellaria baicalensis Georgi., has various pharmacological effects due to its high antioxidant activity. However, no study has yet been conducted on the protective efficacy of baicalein against oxidative stress in Schwann cells. In this study, we evaluated the protective effect of baicalein on DNA damage and apoptosis induced by hydrogen peroxide (H2O2) in HEI193 Schwann cells. For this purpose, HEI193 cells exposed to H2O2 in the presence or absence of baicalein were applied to cell viability assay, immunoblotting, Nrf2-specific small interfering RNA (siRNA) transfection, comet assay, and flow cytometry analyses. Our results showed that baicalein effectively inhibited H2O2-induced cytotoxicity and DNA damage associated with the inhibition of reactive oxygen species (ROS) accumulation. Baicalein also weakened H2O2-induced mitochondrial dysfunction, increased the Bax/Bcl-2 ratio, activated caspase-9 and -3, and degraded poly(ADP-ribose) polymerase. In addition, baicalein increased not only the expression but also the phosphorylation of nuclear factor-erythroid 2 related factor 2 (Nrf2) and promoted the expression of heme oxygenase-1 (HO-1), a critical target enzyme of Nrf2, although the expression of kelch-like ECH-associated protein-1 was decreased. However, the inhibition of Nrf2 expression by transfection with Nrf2-siRNA transfection abolished the expression of HO-1 and antioxidant potential of baicalein. These results demonstrate that baicalein attenuated H2O2-induced apoptosis through the conservation of mitochondrial function while eliminating ROS in HEI193 Schwann cells, and the antioxidant efficacy of baicalein implies at least a Nrf2/HO-1 signaling pathway-dependent mechanism. Therefore, it is suggested that baicalein may have a beneficial effect on the prevention and treatment of peripheral neuropathy induced by oxidative stress.

Isorhamnetin alleviates lipopolysaccharide-induced inflammatory responses in BV2 microglia by inactivating NF-κB, blocking the TLR4 pathway and reducing ROS generation.

Isorhamnetin, which is a flavonoid predominantly found in fruits and leaves of various plants, including Hippophae rhamnoides L. and Oenanthe javanica (Blume) DC, is known to possess various pharmacological effects. However, the anti­inflammatory potential of isorhamnetin remains poorly studied. Therefore, the present study aimed to investigate the inhibitory potential of isorhamnetin against inflammatory responses in lipopolysaccharide (LPS)­stimulated BV2 microglia. To measure the effects of isorhamnetin on inflammatory mediators and cytokines, and reactive oxygen species (ROS) generation, the following methods were used: cell viability assay, griess assay, ELISA, reverse transcriptase­polymerase chain reaction, flow cytometry, western blotting and immunofluorescence staining. The results revealed that isorhamnetin significantly suppressed LPS­induced secretion of pro­inflammatory mediators, including nitric oxide (NO) and prostaglandin E2, without exhibiting significant cytotoxicity. Consistent with these results, isorhamnetin inhibited LPS­stimulated expression of regulatory enzymes, including inducible NO synthase and cyclooxygenase­2 in BV2 cells. Isorhamnetin also downregulated LPS­induced production and expression of pro­inflammatory cytokines, such as tumor necrosis factor­α and interleukin­1ß. The mechanism underlying the anti­inflammatory effects of isorhamnetin was subsequently evaluated; this flavonoid inhibited the nuclear factor (NF)­κB signaling pathway by disrupting degradation and phosphorylation of inhibitor κB­α in the cytoplasm and blocking translocation of NF­κB p65 into the nucleus. In addition, isorhamnetin effectively suppressed LPS­induced expression of Toll­like receptor 4 (TLR4) and myeloid differentiation factor 88. It also suppressed the binding of LPS with TLR4 in BV2 cells. Furthermore, isorhamnetin markedly reduced LPS­induced generation of ROS in BV2 cells, thus indicating a strong antioxidative effect. Collectively, these results suggested that isorhamnetin may suppress LPS­mediated inflammatory action in BV2 microglia through inactivating the NF­κB signaling pathway, antagonizing TLR4 and eliminating ROS accumulation. Further studies are required to fully understand the anti­inflammatory effects associated with the antioxidant capacity of isorhamnetin; however, the findings of the present study suggested that isorhamnetin may have potential benefits in inhibiting the onset and treatment of neuroinflammatory diseases.

Study on the Validity of Surface Electromyography as Assessment Tools for Facial Nerve Palsy.

OBJECTIVES: The purpose of this study was to find out validity of Surface Electromyography(sEMG) compared with Nerve Conduction Study and clinical assessment scale as assessment factors for facial palsy. METHODS: We investigated 50 cases of patients with peripheral facial palsy who had records of sEMG and NCS to check. Then we analyzed the correlation between sEMG and NCS that carried out around 1 week after onset. And we analyzed the correlation between sEMG and clinical assessment scales that were measured three times around 1 week, 3-4 weeks and 5-6 weeks after onset. Clinical assessment scales used in this study were House-brackmann grade, Yanagihara unweighted grading scale and Sunnybrook facial grading system. We used Pearson's correlation for statistical analysis. RESULTS: sEMG and NCS, measured at similar times, were statistically correlated. Especially, the correlation with the forehead region was high. And sEMG and clinical assessment scale, measured at same time, were statistically correlated, especially after 5 weeks from onset. CONCLUSION: According to this study, sEMG is expected to be useful to assessment facial palsy.

Ethanol Extract of Ganoderma lucidum Augments Cellular Anti-oxidant Defense through Activation of Nrf2/HO-1.

OBJECTIVES: The mushroom Ganoderma lucidum has been widely used as a traditional herbal medicine for many years. Although several studies have focused on the anti-oxidative activity of this mushroom, the molecular mechanisms underlying its activity have not yet been clearly established. The present study investigated the cytoprotective effect of ethanol extract of Ganoderma lucidum (EGL) against oxidative stress (hydrogen peroxide, H2O2) and elucidated the underlying mechanisms in a C2C12 myoblast cell line. METHODS: Oxidative stress markers were determined by using the comet assay to measure reactive oxygen species (ROS) generation and deoxyribonucleic acid (DNA) damage. Cell viability and Western blotting analyses were employed to evaluate the cellular response to EGL and H2O2 in C2C12 cells. Transfection with nuclear factor erythroid 2-related factor 2 (Nrf2)-specific small interfering ribonucleic acid (siRNA) was conducted to understand the relationship between Nrf2 expression and H2O2-induced growth inhibition. RESULTS: The results showed that EGL effectively inhibited H2O2-induced growth and the generation of ROS. EGL markedly suppressed H2O2-induced comet-like DNA formation and phosphorylation of histone H2AX at serine 139 (p-γH2AX), a widely used marker of DNA damage, suggesting that EGL prevented H2O2-induced DNA damage. Furthermore, the EGL treatment effectively induced the expression of Nrf2, as well as heme oxygenase-1 (HO-1), with parallel phosphorylation and nuclear translocation of Nrf2 in the C2C12 myoblasts. However, zinc protoporphyrin IX, a HO-1 inhibitor, significantly abolished the protective effects of EGL against H2O2-induced accumulation of ROS and reduced cell growth. Notably, transient transfection with Nrf2-specific siRNA attenuated the cytoprotective effects and HO-1 induction by EGL, indicating that EGL induced the expression of HO-1 in an Nrf2-dependent manner. CONCLUSION: Collectively, these results demonstrate that EGL augments the cellular anti-oxidant defense capacity through activation of Nrf2/HO-1, thereby protecting C2C12 myoblasts from H2O2-induced oxidative cytotoxicity.

Anti-inflammatory potential of total saponins derived from the roots of Panax ginseng in lipopolysaccharide-activated RAW 264.7 macrophages.

Ginseng, the root of Panax ginseng C.A. Meyer (Araliaceae), is a widely known traditional medicine that has been utilized throughout Asia for several thousand years. Ginseng saponins exert various important pharmacological effects regarding the control of a number of diseases. The aim of the present study was to identify the anti-inflammatory effects of total saponins extracted from ginseng (TSG) on lipopolysaccharide (LPS)-stimulated mouse RAW 264.7 macrophages. The inhibitory effects of TSG on LPS-induced nitric oxide (NO) production and LPS-induced tumor necrosis factor-α (TNF-α) and interleukin-1ß (IL-1ß) protein expression were determined by measuring the levels of nitrite and enzyme-linked immunosorbent assays, respectively. Furthermore, the effects of TSG on the mRNA expression levels and localizations of inducible NO synthase (iNOS), IL-1ß and TNF-α, and their upstream signaling proteins, including nuclear factor-κB (NF-κB) and mitogen-activated protein kinases (MAPKs), were investigated by reverse transcription-polymerase chain reaction and western blotting, respectively. Following stimulation with LPS, elevated levels of NO production were detected in RAW 264.7 cells; however, TSG pretreatment significantly inhibited the production of NO (P<0.05), by suppressing the expression of iNOS. In addition, LPS-stimulated TNF-α and IL-1ß production was significantly reduced by TSG (P<0.05). In the LPS-stimulated RAW 264.7 cells, NF-κB was translocated from the cytosol to the nucleus, whilst TSG pretreatment induced the sequestration of NF-κB in the cytosol by inhibiting inhibitor of κB degradation. TSG also contributed to downregulation of MAPKs in LPS-stimulated RAW 264.7 cells. These results suggested that TSG may exert anti-inflammatory activity, and that TSG may be considered a potential therapeutic for the treatment of inflammatory diseases associated with macrophage activation.

A Pilot Study on Single-dose Toxicity Testing of Hominis placenta Pharmacopuncture in Sprague-Dawley Rats.

OBJECTIVES: This study was performed to analyze the toxicity and to find the lethal dose of the test substance Hominis placenta pharmacopuncture when used as a single-dose in 6 week old, male and female Sprague-Dawley (SD) rats. METHODS: All experiments were conducted at Biotoxtech (Chungwon, Korea), an institution authorized to perform non clinical studies, under the regulations of Good Laboratory Practice (GLP). SD rats were chosen for the pilot study. Doses of Hominis placenta pharmacopuncture extracts, 0.125, 0.25 and 0.5 mL, were administered to the experimental group, and 0.5 mL doses of normal saline solution were administered to the control group. This study was conducted under the approval of the Institutional Animal Ethics Committee. RESULTS: No deaths or abnormalities occurred in any of the groups. Also, no significant changes in body weights were observed among the groups, and no significant differences in hematology/biochemistry, necropsy, and histopathology results were noted. Hematologically, some changes in the male rats in two experimental groups were observed, but those changes had no clinical or toxicological meaning because they were not dose dependent. Histopathological tests on the injected parts showed cell infiltration in the male rats in one of the experimental groups; however, that result was due to spontaneous generation and had no toxicological meaning. Therefore, this study showed that Hominis placenta pharmacopuncture had no effect on the injected parts in terms of clinical signs, body weight, hematology, clinical chemistry, and necropsy. CONCLUSION: As a result of single-dose tests of the test substance Hominis placenta pharmacopuncture in 4 groups of rats, the lethal dose for both males and females exceeded 0.5 mL/animal. Therefore, the above findings suggest that treatment with Hominis placenta pharmacopuncture is relatively safe. Further studies on this subject are needed.

Ganoderma Lucidum Pharmacopuncture for Teating Ethanol-induced Chronic Gastric Ulcers in Rats.

OBJECTIVES: The stomach is a sensitive digestive organ that is susceptible to exogenous pathogens from the diet. In response to such pathogens, the stomach induces oxidative stress, which might be related to the development of both gastric organic disorders such as gastritis, gastric ulcers, and gastric cancer, and functional disorders such as functional dyspepsia. This study was accomplished to investigate the effect of Ganoderma lucidum pharmacopuncture (GLP) on chronic gastric ulcers in rats. METHODS: The rats were divided into 4 groups of 8 animals each: the normal, the control, the normal saline (NP) and the GLP groups. In this study, the modified ethanol gastritis model was used. The rats were administrated 56% ethanol orally every other day. The dose of ethanol was 8 g/kg body weight. The normal group received the same amount of normal saline instead of ethanol. The NP and the GLP groups were treated with injection of saline and GLP respectively. The control group received no treatment. Two local acupoints CV12 () and ST36 () were used. All laboratory rats underwent treatment for 15 days. On last day, the rats were sacrificed and their stomachs were immediately excised. RESULTS: Ulcers of the gastric mucosa appeared as elongated bands of hemorrhagic lesions parallel to the long axis of the stomach. In the NP and GLP groups, the injuries to the gastric mucosal injuries were not as severe as they were in the control group. Wound healings of the chronic gastric ulcers was promoted by using GLP and significant alterations of the indices in the gastric mucosa were observed. Such protection was demonstrated by gross appearance, histology and immunehistochemistry staining for Bcl-2-associated X (BAX), B-cell lymphoma 2 (Bcl-2) and Transforming growth factor-beta 1 (TGF-ß1). CONCLUSION: These results suggest that GLP at CV12 and ST36 can provide significant protection to the gastric mucosa against an ethanol induced chronic gastric ulcer.

Cordyceptin induces apoptosis through repressing hTERT expression and inducing extranuclear export of hTERT.

Cordycepin is an adenosine analog originally extracted from Cordyceps militaris that possesses many pharmacological effects including immune activation and antioxidant and antitumor effects. However, the underlying relationship between apoptosis and telomerase activity in response to cordycepin exposure has not been investigated. In this study, we found that cordycepin-induced apoptosis of human leukemia cells (H937 and THP-1 cells) was associated with inactivation of telomerase and downregulation of human telomerase reverse transcriptase (hTERT) as well as the transcription factors c-Myc and Sp1, which are required for basal transcription from the hTERT gene promoter. Cordycepin also attenuated the activation of phosphoinositide-3-kinase (PI3K)/Akt signaling, thereby reducing phosphorylation and nuclear translocation of hTERT. We further showed that the PI3K inhibitor LY29004 significantly decreased telomerase activity in cordycepin-treated cells and increased cordycepin-induced cell death. These findings demonstrate that cordycepin is cytotoxic to human leukemia cells and suppresses telomerase activity through transcriptional and post-translational suppression of hTERT by inactivating the PI3K/Akt signaling pathway.

Hepatoprotective Evaluation of Ganoderma lucidum Pharmacopuncture: In vivo Studies of Ethanol-induced Acute Liver Injury.

OBJECTIVES: Alcohol abuse is a public issue and one of the major causes of liver disease worldwide. This study was aimed at investigating the protective effect of Ganoderma lucidum pharmacopuncture (GLP) against hepatotoxicity induced by acute ethanol (EtOH) intoxication in rats. METHODS: Sprague-Dawley (SD) rats were divided into 4 groups of 8 animals each: normal, control, normal saline pharmacopuncture (NP) and GLP groups. The control, NP and GLP groups received ethanol orally. The NP and the GLP groups were treated daily with injections of normal saline and Ganoderma lucidum extract, respectively. The control group received no treatment. The rats in all groups, except the normal group, were intoxicated for 6 hours by oral administration of EtOH (6 g/kg BW). The same volume of distilled water was administered to the rats in the normal group. Two local acupoints were used: Qimen (LR14) and Taechung (LR3). A histopathological analysis was performed, and the liver function and the activities of antioxidant enzymes were assessed. RESULTS: GLP treatment reduced the histological changes due to acute liver injury induced by EtOH and significantly reduced the increase in the alanine aminotransferase (ALT) enzyme; however, it had an insignificant effect in reducing the increase in aspartate aminotransferase (AST) enzyme. It also significantly ameliorated the superoxide dismutase (SOD) and the catalase (CAT) activities. CONCLUSION: The present study suggests that GLP treatment is effective in protecting against ethanol-induced acute hepatic injury in SD rats by modulating the activities of ethanol-metabolizing enzymes and by attenuating oxidative stress.

Ganoderma lucidum Pharmacopuncture for the Treatment of Acute Gastric Ulcers in Rats.

OBJECTIVES: The gastric ulcer is a common disorder of the stomach and duodenum. The basic physiopathology of a gastric ulcer results from an imbalance between some endogenous aggressive and cytoprotective factors. This study examined whether Ganoderma lucidum pharmacopuncture (GLP) would provide protection against acute gastric ulcers in rats. METHODS: Sprague-Dawley rats were divided randomly into 4 groups of 8 rats each: normal, control, normal saline (NP) and GLP groups. The experimental acute gastric ulcer was induced by using an EtOH/HCl solution and the normal group received the same amount of normal saline instead of ethanol. The NP and the GLP groups were treated once with injections of saline and GLP, respectively. Two local acupoints were used: CV12 () which is the alarm point of the Stomach Meridian, and ST36 (), which is the sea point of the Stomach Meridian. The stomachs from the rats in each group were collected and analyzed for gross appearance and histology. Also, immunohistochemistry staining for BAX, Bcl-2 and TGF-ß1 was performed. RESULTS: Histological observations of the gastric lesions in the control group showed comparatively extensive damage of the gastric mucosa and necrotic lesions had penetrated deeply into the mucosa. The lesions were long, hemorrhagic, and confined to the glandular portions. The lesions were measured microscopically by using the clear depth of penetration into the gastric mucosal surface. The length and the width of the ulcer were measured and the inhibition percentage was calculated. Wound healing of the acute gastric ulcer was promoted by using GLP, and significant alterations of indices in gastric mucosa were observed. Such protection was shown by gross appearance, histology and immunohistochemistry staining for BAX, Bcl-2 and TGF-ß1. CONCLUSION: These results suggest that GLP administered at CV12 and ST36 can provide significant protection to the gastric mucosa against an ethanol-induced acute gastric ulcer.

Anti-inflammatory effects of saponins derived from the roots of Platycodon grandiflorus in lipopolysaccharide­stimulated BV2 microglial cells.

Radix platycodi is the root of Platycodon grandiflorus A. DC, which has been widely used as a food material and for the treatment of a number of chronic inflammatory diseases in traditional oriental medicine. In this study, the anti­inflammatory effects of the saponins isolated from radix platycodi (PGS) on the production of inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated BV2 murine microglial cells were examined. We also investigated the effects of PGS on LPS­induced nuclear factor­κB (NF-κB) activation and phosphoinositide 3-kinase (PI3K)/AKT and mitogen-activated protein kinase (MAPK) signaling pathways. Following stimulation with LPS, elevated nitric oxide (NO), prostaglandin E2 (PGE2) and pro-inflammatory cytokine production was detected in the BV2 microglial cells. However, PGS significantly inhibited the excessive production of NO, PGE2 and pro­inflammatory cytokines, including interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α) in a concentration-dependent manner without causing any cytotoxic effects. In addition, PGS suppressed NF-κB translocation and inhibited the LPS-induced phosphorylation of AKT and MAPKs. Our results indicate that the inhibitory effect of PGS on LPS-stimulated inflammatory response in BV2 microglial cells is associated with the suppression of NF-κB activation and the PI3K/AKT and MAPK signaling pathways. Therefore, these findings suggest that PGS may be useful in the treatment of neurodegenerative diseases by inhibiting inflammatory responses in activated microglial cells.

Ganoderma lucidum ethanol extract inhibits the inflammatory response by suppressing the NF-κB and toll-like receptor pathways in lipopolysaccharide-stimulated BV2 microglial cells.

Ganoderma lucidum is a traditional Oriental medicine that has been widely used as a tonic to promote longevity and health in Korea and other Asian countries. Although a great deal of work has been carried out on the therapeutic potential of this mushroom, the pharmacological mechanisms of its anti-inflammatory actions remain unclear. In this study, we evaluated the inhibitory effects of G. lucidum ethanol extract (EGL) on the production of inflammatory mediators and cytokines in lipopolysaccharide (LPS)-stimulated murine BV2 microglia. We also investigated the effects of EGL on the LPS-induced activation of nuclear factor kappaB (NF-κB) and upregulation of toll-like receptor 4 (TLR4) and myeloid differentiation factor 88 (MyD88). Elevated levels of nitric oxide (NO), prostaglandin E(2) (PGE(2)) and pro-inflammatory cytokine production were detected in BV2 microglia following LPS stimulation. We identifed that EGL significantly inhibits the excessive production of NO, PGE(2) and pro-inflammatory cytokines, including interleukin (IL)-1ß and tumor necrosis factor-α in a concentration-dependent manner without causing cytotoxicity. In addition, EGL suppressed NF-κB translocation and transcriptional activity by blocking IκB degradation and inhibiting TLR4 and MyD88 expression in LPS-stimulated BV2 cells. Our results indicate that the inhibitory effects of EGL on LPS-stimulated inflammatory responses in BV2 microglia are associated with the suppression of the NF-κB and TLR signaling pathways. Therefore, EGL may be useful in the treatment of neurodegenerative diseases by inhibiting inflammatory mediator responses in activated microglia.

Clinical Review of the Effects of Chukyu (spinehealing) Pharmacopuncture in the Treatment of Lumbago and Skelalgia Patients.

OBJECTIVE: The purpose of this study is to report the effects of Chukyu (spine-healing) pharmacopuncture treatment in patients with lumbago and skelalgia. METHODS: This clinical study included 45 patients who were treated for lumbago and skelalgia at the Department of Acupuncture and Moxibusition, Dong-Eui University College of Oriental Medicine, from July 5, 2011, to January 31, 2012. Subjects were randomly divided into two groups: Chukyu (spinehealing)- pharmacopuncture-treated group (experimental group, n = 23) and normal saline-pharmacopuncture-treated group (control group, n = 22). Patients in the experimental group were treated with acupuncture and Chukyu (spine-healing) pharmacopuncture while those in the control group were treated with acupuncture and normal saline pharmacopuncture. To estimate the efficacy of controlling pain, we checked the visual analog scale [VAS], and to estimate the improvement of the symptoms, we evaluated by pain rating scale [PRS] and the Oswestry low-back pain disability index [ODI]. RESULTS: A comparison of the experimental and the control groups showed more significant improvements in the VAS, PRS, and ODI for the experimental group than for the control group. CONCLUSIONS: Chukyu (spine-healing) pharmacopuncture can be used for effective treatment in patients with lumbago and skelalgia.

Comparative study on the effects of bee venom pharmacopuncture according to the treatment method for knee osteoarthritis.

OBJECTIVES: The purpose of this study is to compare the effects of bee venom pharmacopuncture (BVP) therapy according to the methods used to treat knee osteoarthritis (OA): intra-acupoint combined with intra-articular injection, intra-acupoint injection, and intra-articular injection. METHODS: A total of 69 patients were recruited by the Department of Acupuncture & Moxibustion at Dong- Eui Oriental University Hospital from February 1 to July 23, 2012. The patients were assigned to 3 groups: the first group with intra-acupoint combined with intraarticular BVP Injection (the experimental group), the 2nd group with intra-acupoint BVP injection (control groupⅠ), and the 3rd group with intra-articular BVP injection (control groupⅡ). The participants were assigned in the order in which they were recruited. Treatments were done twice a week, for a total of 9 times. The effectiveness was assessed by using the visual analouge scale (VAS) and the Korea Western Ontario and McMaster Universities Osteoarthritis Index (KWOMAC). RESULTS: All three groups exhibited significant VAS and KWOMAC effects. Moreover, the 4 week follow-up after the final treatment showed a persistence of BVP effects. However, when the groups were compared, no statistically significant differences in VAS and KWOMAC were noted, but when improvement was considered, the results showed that intra-articular injection was more effective than intra-acupoint injection. Especially, intra-acupoint combined with intra-articular injection was the most effective among the three treatments. CONCLUSIONS: Combining intra-acupoint with intraarticular injection, depending on the patient's symptoms, may produce better results when conservatively treating knee OA.

Rehmannia Glutinosa Pharmacopuncture Solution Regulates Functional Activation, FcεRI Expression, and Signaling Events in Mast Cells.

OBJECTIVES: Rehmannia glutinosa pharmacopuncture solution (RGPS) was investigated to determine both its anti-allergic inflammatory effects on mast cells and its detailed mechanism of actions. METHODS: We investigated whether RGPS suppress cytokines, enzymes, FcεRI expression and FcεRImediated signaling in RBL-2H3 cells stimulated with anti-DNP IgE/DNP-HSA. The suppressive effects of RGPS on the levels of cytokines such as IL-1ß, IL-6 and GM-CSF were measured using emzyme-linked immunospecific assay (ELISA). The mRNA expression levels of cytokines, enzymes (HDC2, COX-1, COX-2 and 5LO) and FcεRI αßγsubunits were measured using reverse transcription polymerase chain reaction (RTPCR) method. The activation of FcεRI-mediated signaling was examined using Western blot analyses. RESULTS: RGPS suppressed production of proinflamm-atory cytokines (IL-1ß, IL-6, and GM-CSF) in stimulated RBL-2H3 cells significantly (p< 0.05). RGPS also suppressed mRNA expression of inflammatory enzymes (HDC2, COX-1, COX-2, 5LO). In addition, mRNA expression levels of FcεRIα, FcεRIßand FcεRIγ were lowered by treatment with RGPS. Finally, RGPS prevented phosphrylation of Lyn, Syk, LAT, Gab2, PLC γ1/2, PI3K, Akt, cPLA2 and IκBα. CONCLUSIONS: RGPS effectively suppresses mast cell activations such as degranulation and inflammatory response via down-regulation of the FcεRI-mediated signaling pathways in IgE/Ag-stimulated mast cells.