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.

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.

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.

Anti-invasive activity of ethanol extracts of Ganoderma lucidum through tightening of tight junctions and inhibition of matrix metalloproteinase activities in human gastric carcinoma cells.

This study investigated the effect of ethanol extracts of Ganoderma lucidum (EGL) on the correlation between tightening of the tight junctions (TJs) and the anti-invasive activity in human gastric adenocarcinoma AGS cells to elucidate further the possible anticancer mechanisms that G lucidum exerts. Within the concentrations of EGL that were not cytotoxic, EGL markedly inhibited the cell motility and invasiveness in a concentration-dependent manner. The activities of matrix metalloproteinases (MMP)-2 and MMP-9 in AGS cells were dose-dependently inhibited by treatment with EGL, and this was correlated with a decrease in expression of their mRNA and proteins and the upregulation of the expression of the tissue inhibitors of metalloproteinases. The anti-invasive activity of EGL was also found to be associated with the increased tightness of the TJ, which was demonstrated by an increase in transepithelial electrical resistance. Additionally, EGL repressed the levels of the claudin family members, which are major components of TJs that play a key role in the control and selectivity of paracellular transport. Furthermore, the levels of E-cadherin, a type I transmembrane glycoprotein, were inhibited by EGL treatment, however, those of snail, an epithelial to mesenchymal transition regulator and zinc finger transcription factor, were concentration-dependently increased in response to EGL treatment. Although further studies are needed, the present study indicates that TJs and MMPs are crucial targets of EGL-induced anti-invasiveness in human gastric cancer AGS cells.

Sa-Ahm Five Element acupuncture.

This study aimed to review the clinical basis for Sa-Ahm Five Element acupuncture. This form of acupuncture uses the Five-Shu acupoints and the tonification-sedation treatments based on the creation and control cycles of the Five Elements. A total of 28 books and papers from the ancient "Nan-Ching" to the modern "Medical Acupuncture" were used to study clinical practices. Sa-Ahm Five Element acupuncture could be practiced in different ways depending upon differential diagnoses. These diagnoses include theories of excess and deficiency of Yin and Yang, seven emotions, ZangFu (organ, viscera), and comparing pulse diagnosis and meridian therapy to meridian palpation. Clinical trials and guidelines for the practice of Sa-Ahm acupuncture should be created to allow for a more evidence-based clinical approach to using this technique.

Induction of apoptosis by ethanol extracts of Ganoderma lucidum in human gastric carcinoma cells.

Ganoderma lucidum, a well-known medicinal mushroom, is highly valued and commonly used in Oriental medicine. Although recent experimental data has revealed the proapoptotic potency of G. lucidum extracts, the underlying mechanisms of this apoptotic activity have not yet been studied in detail. In the present study, the effects of ethanol extracts of G. lucidum (EGL) on the growth of an AGS human gastric carcinoma cell line were investigated. We found that EGL treatment resulted in a dose and time-dependent significant decrease in the viability of AGS cells. This decreased viability was caused by apoptotic cell death, with observed chromatin condensation and an accumulation of apoptotic fraction. EGL treatment induced the expression of death receptor-related proteins such as death receptor 5 and tumor necrosis factor-related apoptosis-inducing ligand, which further triggered the activation of caspase-8 and the cleavage of Bid. In addition, the increase in apoptosis that was induced by EGL was correlated with activation of caspase-9 and -3, downregulation of IAP family proteins such as XIAP and survivin, and concomitant degradation of poly (ADP-ribose) polymerase. Moreover the activity of Akt was downregulated in EGL-treated cells, and the phosphatidylinositol-3 kinase/ Akt inhibitor LY294002 sensitized the cells to EGL-induced apoptosis. The results indicated that EGL induces the apoptosis of AGS cells through a signaling cascade of death receptor-mediated extrinsic, as well as mitochondria-mediated intrinsic, caspase pathways which are associated with inactivation of the Akt signal pathway.

A study of the Sa-Ahm Five Element acupuncture theory.

This study is a review of the theoretical basis of Sa-Ahm Five Element acupuncture devised about 360 years ago. A total of 21 books and papers ranging from the ancient Huang Di Nei Jing to modern biomedical acupuncture for pain management were researched in relation to the Five Shu points. Gao-Wu, in the Chinese Ming Dynasty, used the Five Shu points for the first time based on the creation cycle as the tonification and sedation treatment, termed the "tonification and sedation treatment of self meridian". Since then, and for no particular reason, this method has been rarely used until Sa-Ahm's new doctrine, which includes the concept of the destruction cycle, was asserted. Sa-Ahm Five Element acupuncture is a method in which the Five Shu points are used from the viewpoints of the simultaneous tonification and sedation methods that are based on the promotion and control cycles. Although it is currently the most utilized method in accordance with the practitioner's points, this method is in need of designated guidelines by which Sa-Ahm acupuncture can be practiced effectively.