Cordycepin Inhibits Enterovirus A71 Replication and Protects Host Cell from Virus-Induced Cytotoxicity through Adenosine Action Pathway.

Enterovirus A71 (EV-A71) infection typically causes mild illnesses, such as hand-foot-and-mouth disease (HFMD), but occasionally leads to severe or fatal neurological complications in infants and young children. Currently, there is no specific antiviral treatment available for EV-A71 infection. Thus, the development of an effective anti-EV-A71 drug is required urgently. Cordycepin, a major bioactive compound found in Cordyceps fungus, has been reported to possess antiviral activity. However, its specific activity against EV-A71 is unknown. In this study, the potency and role of cordycepin treatment on EV-A71 infection were investigated. Results demonstrated that cordycepin treatment significantly reduced the viral load and viral ribonucleic acid (RNA) level in EV-A71-infected Vero cells. In addition, EV-A71-mediated cytotoxicity was significantly inhibited in the presence of cordycepin in a dose-dependent manner. The protective effect can also be extended to Caco-2 intestinal cells, as evidenced by the higher median tissue culture infectious dose (TCID50) values in the cordycepin-treated groups. Furthermore, cordycepin inhibited EV-A71 replication by acting on the adenosine pathway at the post-infection stage. Taken together, our findings reveal that cordycepin could be a potential antiviral candidate for the treatment of EV-A71 infection.

Qing Yan Li Ge Tang Induces Apoptosis in Human OEC-M1 Oral Cancer Cells.

Background: Since most patients with oral cancer do not benefit from current treatments, new therapeutic strategies or drugs must be developed to improve patient prognosis. Qing Yan Li Ge Tang (QYLGT), a Chinese herbal medicine, is known for its anticancer activity. This study aimed to investigate whether QYLGT has anticancer effects on human OEC-M1 oral cancer cells. Methods: To evaluate whether QYLGT affects viability, morphology, and colony formation ability of the OEC-M1 cells, the 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, morphology study, and colony formation assay were performed, respectively. Each assay was carried out in triplicate, and the whole set of experiments was performed three times independently. To investigate whether QYLGT induces apoptotic effects in OEC-M1 cells, the enzyme-linked immunosorbent (ELISA) was carried out to quantify cytokeratin 18 fragment (an apoptosis marker). Each assay was carried out in triplicate, and the whole set of experiments was performed three times independently. The immunoblotting assay was performed to detect the protein expression after QYLGT treatment. The whole set of experiments was performed two times independently. Results: The results from the MTT and colony formation assays indicate that QYLGT inhibited the cell viability and clonogenic growth capacity of OEC-M1 cells. The morphology study shows that QYLGT increased plasma membrane blebbing in OEC-M1 clles. The results of ELISA and an immunoblotting assay show that QYLGT increased cytokeratin 18 fragment release and poly ADP-ribose polymerase cleavage (another apoptosis marker) in OEC-M1 cells. In addition, the results from immunoblotting assay show that QYLGT also activated apoptotic executor proteins, including caspase-8, caspase-9, and caspase-3, and the results of ELISA indicate that treatment with the pan-caspase inhibitor, Z-VAD-FMK, inhibited QYLGT-induced cytokeratin 18 fragment release. These results indicate that QYLGT inhibited cell viability in OEC-M1 cells and induced OEC-M1 apoptosis through caspase activation. Additionally, QYLGT-activated c-Jun N-terminal kinase, extracellular signal-regulated kinase, p38 mitogen-activated protein kinase, and nuclear factor-kappa B (NF-κB), and the related inhibitors, including SP600125, PD184352, SB202190, and Bay11-7082, were used to confirm which signaling was involved in QYLGT-induced apoptosis. Moreover, only Bay11-7082, the NF-κB inhibitor, could suppress QYLGT-induced the release of cytokeratin 18 fragments from OEC-M1 cells. Conclusions: QYLGT induced apoptosis in OEC-M1 cells via the NF-κB pathway.

Cordycepin Induces Apoptosis through JNK-Mediated Caspase Activation in Human OEC-M1 Oral Cancer Cells.

Cordycepin, a bioactive compound extracted from Cordyceps sinensis, can induce apoptosis in human OEC-M1 oral cancer cells. However, the exact mechanism is still unclear. The present study aimed to investigate the underlying mechanism of cordycepin-induced apoptosis in OEC-M1 cells. Following treatment with cordycepin, apoptosis was examined and quantified using a DNA laddering assay and a cytokeratin 18 fragment enzyme-linked immunosorbent assay, respectively. Expressions of mitogen-activated protein kinases (MAPKs) and apoptosis-related proteins were detected by the western blot analysis. Our results show that a pan-caspase inhibitor, Z-VAD-FMK, could significantly inhibit cordycepin-induced apoptosis in OEC-M1 cells. In addition, treatment with cordycepin not only activated caspase-8, caspase-9, and caspase-3 but also induced Bid and poly ADP-ribose polymerase cleavages. Furthermore, cordycepin also induced the activation of c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase, and p38 MAPKs. Among MAPKs, activation of JNK solely contributed to cordycepin-induced apoptosis with the activation of caspase-8, caspase-9, and caspase-3 and cleavage of PARP. Taken together, the present study demonstrated that cordycepin activated JNK and caspase pathways to induce apoptosis in OEC-M1 cells.

Qing Yan Li Ge Tang, a Chinese Herbal Formula, Induces Autophagic Cell Death through the PI3K/Akt/mTOR Pathway in Nasopharyngeal Carcinoma Cells In Vitro.

Since a portion of patients with nasopharyngeal carcinoma (NPC) do not benefit much from current standard treatments, it is still needed to discover new therapeutic drugs to improve the prognosis of the patients. Considering that Chinese traditional medicine plays a role in inhibiting tumor progression, in this study, we aimed to investigate whether a Chinese herbal formula, Qing Yan Li Ge Tang (QYLGT), has the anticancer activity in NPC cells and explore the underlying mechanism as well. MTT assay, colony formation assay, immunoblotting assay, and DNA laddering assay were performed to assess cell viability, cell colony formation, protein expression, and DNA fragmentation, respectively. Results show that QYLGT was able to inhibit the cell viability and decrease colony formation ability in NPC cells. QYLGT could also increase the formation of intracellular vacuoles and induce the autophagy-related protein expressions, including Atg3, Atg6, and Atg12-Atg5 conjugate in NPC cells. Treatment with an autophagy inhibitor, 3-methyladenine, could significantly recover QYLGT-inhibited cell viability of NPC cells. In addition, QYLGT did not significantly induce apoptosis in NPC cells. We also found that QYLGT had the ability to activate phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of the rapamycin (mTOR) pathway. Treatment with PI3K inhibitors, LY294002 and wortmannin, or mTOR inhibitors, rapamycin and Torin 1, could not only recover QYLGT-inhibited cell viability of NPC cells but also inhibit Atg3 expression. Taken together, our results demonstrated that QYLGT could induce autophagic cell death in NPC cells through the PI3K/Akt/mTOR pathway.

Phytochemicals from Polyalthia Species: Potential and Implication on Anti-Oxidant, Anti-Inflammatory, Anti-Cancer, and Chemoprevention Activities.

Polyalthia belong to the Annonaceae family and are a type of evergreen tree distributed across many tropical and subtropical regions. Polyalthia species have been used long term as indigenous medicine to treat certain diseases, including fever, diabetes, infection, digestive disease, etc. Recent studies have demonstrated that not only crude extracts but also the isolated pure compounds exhibit various pharmacological activities, such as anti-oxidant, anti-microbial, anti-tumor, anti-cancer, etc. It is known that the initiation of cancer usually takes several years and is related to unhealthy lifestyle, as well as dietary and environmental factors, such as stress, toxins and smoking. In fact, natural or synthetic substances have been used as cancer chemoprevention to delay, impede, or even stop cancer growing. This review is an attempt to collect current available phytochemicals from Polyalthia species, which exhibit anti-cancer potentials for chemoprevention purposes, providing directions for further research on the interesting agents and possible clinical applications.

The Role of Autophagy in Anti-Cancer and Health Promoting Effects of Cordycepin.

Cordycepin is an adenosine derivative isolated from Cordyceps sinensis, which has been used as an herbal complementary and alternative medicine with various biological activities. The general anti-cancer mechanisms of cordycepin are regulated by the adenosine A3 receptor, epidermal growth factor receptor (EGFR), mitogen-activated protein kinases (MAPKs), and glycogen synthase kinase (GSK)-3ß, leading to cell cycle arrest or apoptosis. Notably, cordycepin also induces autophagy to trigger cell death, inhibits tumor metastasis, and modulates the immune system. Since the dysregulation of autophagy is associated with cancers and neuron, immune, and kidney diseases, cordycepin is considered an alternative treatment because of the involvement of cordycepin in autophagic signaling. However, the profound mechanism of autophagy induction by cordycepin has never been reviewed in detail. Therefore, in this article, we reviewed the anti-cancer and health-promoting effects of cordycepin in the neurons, kidneys, and the immune system through diverse mechanisms, including autophagy induction. We also suggest that formulation changes for cordycepin could enhance its bioactivity and bioavailability and lower its toxicity for future applications. A comprehensive understanding of the autophagy mechanism would provide novel mechanistic insight into the anti-cancer and health-promoting effects of cordycepin.

Induction of mitochondrial-dependent apoptosis by essential oil of Toona sinensis root through Akt, mTOR and NF-κB signalling pathways in human renal cell carcinoma cells.

Natural products have long been considered as a kind of complementary medicine. In this study, we investigate the apoptotic effect of essential oils of Toona sinensis roots (TSR) on human clear cell renal cell carcinomas (ccRCC). The sesquiterpene content of TSR essential oil was determined via GC/MS analysis. TSR decreased ccRCC cell viabilities, inducing ROS generation and reduction of the mitochondrial membrane potential. Moreover, TSR inhibited Bcl-2 and Hsp90 expression but increased PARP-1 cleavage and cytochrome c release. Akt, mTOR and NF-κB phosphorylation and HIF-α expression were all inhibited, which likely contributed to the anti-proliferative and anti-adhesive effects of TSR.

16-Hydroxycleroda-3, 13-dien-15, 16-olide inhibits the proliferation and induces mitochondrial-dependent apoptosis through Akt, mTOR, and MEK-ERK pathways in human renal carcinoma cells.

BACKGROUND: Renal cell carcinoma (RCC) is well known that it cannot be treated with traditional chemotherapy or radiotherapy. 16-Hydroxycleroda-3,13-dien-15,16-olide (CD), isolated from Polyalthia longifolia Benth. & Hook. f. var. pendula had been reported to display significant efficacy against cancer cell lines. PURPOSE: To determine the anti-tumour activities of CD in two clear cell type RCC (ccRCC) cell lines (A-498 and 786-O). In addition, the underlying mechanisms were also examined. METHODS: The cell viabilities of CD-treated ccRCC cells were examined by MTT assay. The apoptotic features were confirmed by acridine orange and ethidium bromide staining. 2',7'-dichlorofluorescin diacetate was used to check reactive oxygen species (ROS) involvement. Mitochondria membrane potential (MMP) were determined by using fluorescent dyes, rhodamine 123 and 5',6,6'-tetrachloro-1,1',3,3'-tetraethyl benzimidazolylcarbocyanine iodide (JC-1). Proapoptotic, anti-apoptotic proteins and intracellular signaling molecules involved in CD-induced apoptosis were examined by Western blot analysis. RESULTS: CD inhibited both 786-O and A-498 cell proliferation and induced a series apoptotic characteristics expressions, ROS accumulation, caspase-3 activation as well as poly-(ADP-ribose) polymerase cleavage in both ccRCC cells. Additionally, CD caused MMP reduction and cytochrome c release from mitochondria as well as inhibition of anti-apoptotic proteins, including B cell lymphoma 2 and heat shock protein 70. Mechanically, we address that CD suppressed cell proliferation and induced apoptosis via induction of FOXO3a as well as decreased phosphorylation of Akt, mTOR, MEK/ERK and their downstream molecules, cMyc and hypoxia inducible factor 2α expression in a concentration- and time-dependent trend. CONCLUSION: CD caused cell death through ROS overproduction and induction of mitochondria-dependent apoptotic pathway in ccRCC cells that accompanied with multiple oncogenic signals inactivation.

Aqueous Extracts of Toona sinensis Leaves Inhibit Renal Carcinoma Cell Growth and Migration Through JAK2/stat3, Akt, MEK/ERK, and mTOR/HIF-2α Pathways.

Toona sinensis (TS) is a type of deciduous tree, which is distributed widely in Asia and used as a traditional herb medicine. Previously, we demonstrated that aqueous extracts of TS leaves (TSL-1) induce apoptosis in two clear types of human renal carcinoma cells (ccRCC) via mitochondria-dependent pathway. In this study, we further investigated the more detailed mechanism of TSL-1-induced antitumor effects on ccRCCs. TSL-1 treatment arrested ccRCC cells in G0/G1 phase through the decrease of cyclin D1, cyclin-dependent kinase (CDK)2, and CDK4 as well as induction of p53 and FOXO3a protein expressions. On the other hand, the inhibitory effects of TSL-1 on migration were also observed in 786-O and A-498 cells. Mechanically, we presented that TSL-1 could suppress cell cycle progression and motility via inhibiting the phosphorylation of JAK2/stat3, Akt, MEK/ERK, and mTOR in a concentration- and time-dependent manner. Moreover, we found that TSL-1 inhibited p21, HIF-2α, c-Myc, VEGF, and MMP9 protein expressions in both cell lines. In conclusion, these findings suggested that TS-induced apoptosis and its antimigration activity in ccRCC cells were accompanied by inactivation of several oncogenic pathways.

Apoptotic effect of cisplatin and cordycepin on OC3 human oral cancer cells.

OBJECTIVE: To evaluate apoptotic effects of cisplatin and cordycepin as single agent or in combination with cytotoxicity in oral cancer cells. METHODS: The influences of cisplatin (2.5 µg/mL) and/or cordycepin treatment (10 or 100 µmol/L) to human OC3 oral cancer cell line were investigated by morphological observation for cell death appearance, methylthiazoletetrazolium (MTT) assay for cell viability, flow cytometry assay for cell apoptosis, and Western blotting for apoptotic protein expressions. RESULTS: Data demonstrated that co-administration of cisplatin (2.5 µg/mL) and cordycepin (10 or 100 µmol/L) resulted in the enhancement of OC3 cell apoptosis compared to cisplatin or cordycepin alone treatment (24 h), respectively (P <0.05). In flow cytometry assay, percentage of cells arrested at subG1 phase with co-treatment of cordycepin and cisplatin (30%) was significantly higher than cisplatin (5%) or cordycepin (12%) alone group (P <0.05), confirming a synergistically apoptotic effect of cordycepin and cisplatin. In cellular mechanism study, co-treatment of cordycepin and cisplatin induced more stress-activated protein kinase/Jun terminal kinase (JNK), the expressions of caspase-7, and the cleavage of poly ADP-ribose polymerase (PARP) as compared to cisplatin or cordycepin alone treatment (P <0.05). CONCLUSION: Cisplatin and cordycepin possess synergistically apoptotic effect through the activation of JNK/caspase-7/PARP pathway in human OC3 oral cancer cell line.

Cordycepin stimulated steroidogenesis in MA-10 mouse Leydig tumor cells through the protein kinase C Pathway.

Cordycepin (3'-deoxyadenosine) is an adenosine analogue isolated from Cordyceps sinensis , which is a Chinese herbal medicine known to have many benefits, including adjustment of the physical condition, an anticancer effect, and enhancement of sexual performance. It was previously demonstrated that cordycepin could simultaneously activate steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells. However, the mechanism remains elusive. Thus, aim of the present study was to investigate the steroidogenic and apoptotic mechanism of cordycepin in MA-10 cells. MA-10 cells were treated with cordycepin at various dosages and time courses plus different protein kinase inhibitors. Steroid production, protein expression, and cell viability were then determined. Results illustrated that cordycepin stimulated MA-10 cell steroidogenesis in dose- and time-dependent relationships. However, cordycepin could not induce steroidogenic acute regulatory (StAR) protein expression. However, cordycepin did activate the phospholipase C/protein kinase C (PLC/PKC), but not PKA and PI3K, pathway to induce MA-10 cell steroidogenesis. Moreover, cordycepin could stimulate the phosphorylation of PKC, extracellular signal-regulated kinase 1/2 (ERK1/2), and c-Jun N-terminal kinase (c-JNK), but not p38, in MA-10 cells. In addition, cordycepin could activate the PKC pathway to induce MA-10 cell death, and this death effect was not caused by cordycepin-stimulated progesterone from MA-10 cells. In conclusion, cordycepin stimulated intracellular PLC/PKC and MAPK signal transduction pathways to induce steroidogenesis and cell death in MA-10 mouse Leydig tumor cells.

The Effect of Cordycepin on Steroidogenesis and Apoptosis in MA-10 Mouse Leydig Tumor Cells.

Cordycepin is a natural pure compound extracted from Cordyceps sinensis (CS). We have demonstrated that CS stimulates steroidogenesis in primary mouse Leydig cell and activates apoptosis in MA-10 mouse Leydig tumor cells. It is highly possible that cordycepin is the main component in CS modulating Leydig cell functions. Thus, our aim was to investigate the steroidogenic and apoptotic effects with potential mechanism of cordycepin on MA-10 mouse Leydig tumor cells. Results showed that cordycepin significantly stimulated progesterone production in dose- and time-dependent manners. Adenosine receptor (AR) subtype agonists were further used to treat MA-10 cells, showing that A(1), A( 2A ), A( 2B ), and A(3), AR agonists could stimulate progesterone production. However, StAR promoter activity and protein expression remained of no difference among all cordycepin treatments, suggesting that cordycepin might activate AR, but not stimulated StAR protein to regulate MA-10 cell steroidogenesis. Meanwhile, cordycepin could also induce apoptotic cell death in MA-10 cells. Moreover, four AR subtype agonists induced cell death in a dose-dependent manner, and four AR subtype antagonists could all rescue cell death under cordycepin treatment in MA-10 cells. In conclusion, cordycepin could activate adenosine subtype receptors and simultaneously induce steroidogenesis and apoptosis in MA-10 mouse Leydig tumor cells.

Cordycepin Induced MA-10 Mouse Leydig Tumor Cell Apoptosis through Caspase-9 Pathway.

In the present study, the apoptotic effect of cordycepin on MA-10 cells, a mouse Leydig tumor cell line, was investigated. Results demonstrated that the number of rounding-up cell increased by cordycepin (10 µM to 5 mM for 24 h), and cells with plasma membrane blebbing could be observed by 100 µM cordycepin. In viability test, MA-10 cell surviving rate significantly decreased as the dosage (10 µM to 5 mM) and duration (3-24 h) of cordycepin treatment increased (P < 0.05). Cordycepin at 100 µM and 1 mM for 24 h treatment induced significant DNA fragmentation (P < 0.05). In addition, the percentage of G1 and G2/M phase cell significantly declined by cordycepin (100 µM and 1 mM) for 24 h treatment, while the percentages of subG1 phase cell increased by 100 µM and/or 1 mM cordycepin in 6, 12 and 24 h treatments (P < 0.05), respectively, which highly suggested that cordycepin induced MA-10 cell apoptosis. In mechanism study with the treatments of caspases, c-Jun NH(2) terminal kinase (JNK) or reactive oxygen species (ROS) inhibitors plus cordycepin for 24 h, only caspases inhibitor suppressed subG1 phase in MA-10 cells. Moreover, western blotting results showed that cordycepin induced caspase-9, -3 and -7 protein expressions, but not caspase-8, in time- and dose-dependent manners. In conclusion, cordycepin induced apoptosis in MA-10 mouse Leydig tumor cells through a caspase-9 and -3 and -7 dependent pathway.

Regulatory mechanisms of Cordyceps sinensis on steroidogenesis in MA-10 mouse Leydig tumor cells.

Cordyceps sinensis (CS) is an herbal medicine that increases steroidogenesis in Leydig cells and improves male reproductive dysfunction. We have found that CS stimulates Leydig cell steroidogenesis through the protein kinase A and protein kinase C signaling pathways. In the present study, we sought to determine the mechanisms of CS-stimulated steroidogenesis in MA-10 mouse Leydig tumor cells. Using pharmacological approaches, we found that de novo protein synthesis, protein transcription, a calcium signal, and a mitochondria electrochemical gradient were required for CS-stimulated steroidogenesis in MA-10 cells. mRNA expression of steroidogenic acute regulatory protein was activated by CS. However, CS had an adversary effect on P450 side-chain cleavage enzyme activity, but not in 3ß-hydroxysteroid dehydrogenase enzyme, in regulating MA-10 cell steroidogenesis. In conclusion, de novo protein synthesis, increased steroidogenic acute regulatory protein mRNA expression, and the mitochondria electrochemical gradient were involved in CS-stimulated steroidogenesis in MA-10 cells.

Sound exposure accelerates reflex emergence and development in young rats.

Early sensory experience affects brain development. In rats, most somatic reflexes are not expressed at birth but may take as long as 2 weeks to emerge. Whether sensory enrichment during this early period affects reflex maturation remains unknown. Here, we exposed rat pups to a pure tone (4kHz, 65dB SPL, 8h/day) with their nursing mother during the first 3 postnatal weeks and measured the times when reflexes appeared on the basis of video recordings. Sound exposure accelerated by about 15% the appearance of all reflexes assessed (righting, cliff avoidance, vibrissa placing, negative geotaxis and auditory startle, p<0.001). In addition, sound exposure accelerated the appearance of developmental characteristics: incisor eruption, ear unfolding and eye opening. These changes occurred concomitantly with an increase in pups' body and brain weights, together with a dramatic increase in fluid intake of the nursing mother. These findings are the first evidence that early sound exposure, even before opening of ear canals, accelerates reflex development. We speculate that the observed changes could involve the nursing mother.

The effect of midazolam on mouse Leydig cell steroidogenesis and apoptosis.

The peripheral-type benzodiazepine receptor (PBR), a putative receptor in Leydig cells, modulates steroidogenesis. Since benzodiazepines are commonly used in regional anesthesia, their peripheral effects need to be defined. Therefore, this study set out to investigate in vitro effects of the benzodiazepine midazolam (MDZ) on Leydig cell steroidogenesis, and the possible underlying mechanisms. The effects of MDZ on steroidogenesis in primary mouse Leydig cells and MA-10 Leydig tumor cells were determined by radioimmunoassay. PBR, P450scc, 3beta-HSD and StAR protein expression induced by MDZ was determined by Western blotting. Inhibitors of the signal transduction pathway and a MDZ antagonist were used to investigate the intracellular cascades activated by MDZ. In both cell types, MDZ-stimulated steroidogenesis in dose- and time-dependent manners, and induced the expression of PBR and StAR proteins, but had no effect on P450scc and 3beta-HSD expressions. Moreover, H89 (PKA inhibitor) and GF109203X (PKC inhibitor) attenuated MDZ-stimulated steroid production. Interestingly, the MDZ antagonist (flumazenil) did not decrease MDZ-induced steroid production in both cell types. These results highly indicated that MDZ-induced steroidogenesis in mouse Leydig cells via PKA and PKC pathways, along with the expression of PBR and StAR proteins. In addition, MDZ at high dosages induced rounding-up, membrane blebbing, and then death in MA-10 cells. In conclusion, midazolam could induce Leydig tumor cell steroidogenesis, and high dose of midazolam could induce apoptosis in Leydig tumor cells.

The spatial and segmental innervation of somatic acupoint - a study of canine Shen-Shu point (BL-23).

Although an acupuncture needle penetrates the skin, subcutaneous tissue, and underlying muscle, the most effective locus for the somatic acupoint on the needle path is not well established. We therefore investigated the sensory innervations of tissues in the needle path of the canine Shen-Shu point and evaluated their roles in initiating an acupunctural signal. Horseradish peroxidase solution was injected at all three levels within the acupoint. Only a few peroxidase-positive neurons were observed in the L1 dorsal root ganglion following intradermal injection. Following subcutaneous injection, peroxidase-labeled neurons were detected extending from spinal levels T10 to L2, with maximal labeling at T12 (46.3%). Approximately 95% of positive neurons were at spinal levels T11, T12, T13, and L1. As a result of an intramuscular injection, labeled neurons were observed at spinal levels T12 to L3, with most labeling occurring at L1 (39.9%). Approximately 95% of positive neurons were at spinal levels T13, L1, and L2. The results suggest that most afferent terminals are in the subcutaneous tissue rather than the muscular tissue, with an approximate ratio of 3.75:1. The data provide solid evidence that sensory innervation to a somatic acupoint is confined to a spinal segment and spatially organized, and we speculate that to cause a maximum effect, the centripetally transmitted signal from needling a somatic acupoint is spatio-segmental and divergently amplified.

Sesame oil attenuates acute iron-induced lipid peroxidation-associated hepatic damage in mice.

Acute iron intoxication from the accidental ingestion of iron-containing preparations is one important cause of death in children. The aim of this study was to investigate the protective effect of sesame oil on acute iron-induced lipid peroxidation (LPO) and hepatic injury in mice. Acute iron intoxication was induced by giving ferric nitrilotriacetate to mice. Hepatic function was assessed using blood biochemistry. Free radicals were determined using a high-performance chemiluminescence analyzer. Ferric nitrilotriacetate increased serum ferrous (Fe) and LPO levels, and induced acute hepatic injury. Sesame oil (a) dose-dependently decreased acute iron-induced LPO and hepatic injury, (b) reduced acute iron-associated hydroxyl radical and superoxide anion generation, and (c) inhibited the activity of xanthine oxidase in acute iron intoxication. Thus, sesame oil might ameliorate LPO and acute hepatic injury by inhibiting xanthine oxidase-initiated superoxide anion generation, thereby reducing hydroxyl radical production, at least partially, in acutely iron-intoxicated mice.

The regulatory mechanism of Tremella mesenterica on steroidogenesis in MA-10 mouse Leydig tumor cells.

Tremella mesenterica (TM), a yellow jelly mushroom, has been traditionally used as tonic food to improve body condition in Chinese society for a long time. We have previously demonstrated that TM reduced in vitro hCG-treated steroidogenesis in MA-10 mouse Leydig tumor cells without any toxicity effect. In the present study, the mechanism how TM suppressed hCG-treated steroidogenesis in MA-10 cells was investigated. MA-10 cells were treated with vehicle, human chorionic gonadotropin (hCG, 50 ng/ml), or different reagents with or without TM to clarify the effects. TM significantly suppressed progesterone production with the presences of forskolin (10 and 100 microM) or dbcAMP (0.5 and 1mM), respectively, in MA-10 cells (p<0.05), which indicated that TM suppressed steroidogenesis after PKA activation along the signal pathway. Beyond our expectation, TM induced the expression of steroidogenic acute regulatory (StAR) protein with or without hCG treatments. However, TM profoundly decreased P450 side chain cleavage (P450scc) and 3beta-hydroxysteroid dehydrogenase (3beta-HSD) enzyme activities without any influences on the expression of both enzymes. These inhibitions on steroidogenic enzyme activities might counteract the stimulation of StAR protein expression. In conclusion, results suggest that TM suppressed hCG-treated steroidogenesis in MA-10 cells by inhibiting PKA signal pathway and steroidogenic enzyme activities.

Effects of ingested fruiting bodies, submerged culture biomass, and acidic polysaccharide glucuronoxylomannan of Tremella mesenterica Retz.:Fr. on glycemic responses in normal and diabetic rats.

Mushroom polysaccharides have been shown to regulate glucose metabolism. Using male Wistar rats injected with saline (normal rats), streptozotocin (STZ-NT rats), or streptozotocin plus nicotinamide (STZ+NT rats), we investigated the hypoglycemic activity of orally ingested fruiting bodies (FB), submerged culture biomass (CM), or the acidic polysaccharide glucuronoxylomannan (GXM) of Tremella mesenterica, an edible jelly mushroom. Our results demonstrated that FB ingestion significantly attenuated the elevated blood glucose levels in an oral glucose tolerance test (OGTT) in STZ-NT rats. However, in STZ+NT rats, FB, CM, and GXM ingestion significantly attenuated the increases in food and water intake, 2-h postprandial blood glucose concentrations, and blood glucose levels in OGTT. Moreover, FB and GXM ingestion significantly decreased serum concentration of fructosamine in STZ+NT rats. Our results indicated that T. mesenterica might be developed as a potential oral hypoglycemic agent or functional food for diabetic patients and for persons with high risk for diabetes mellitus.