Chemical Composition and Chronic Toxicity of Disc-Cultured Antrodia cinnamomea Fruiting Bodies.

Antrodia cinnamomea (AC) is a popular fungus for use as folk medicine in health maintenance and disease prevention and treatment. Disc culture is a novel technique for producing AC fruiting bodies. This study aimed to investigate the bioactive components and toxicological properties of disc-cultured AC fruiting body powders (ACP) in rats. The HPLC technique was used to quantify the composition of bioactive triterpenoids in ACP. Toxicological properties were evaluated on male and female Sprague-Dawley rats receiving ACP orally at 200, 600, and 1000 mg/kg body weight for 90 days; the control group received only distilled water. The results show that ACP contained seven important AC index compounds, namely antcins A, B, C, K, and H, dehydrosulphurenic acid, and dehydroeburicoic acid. At the tested doses, oral ACP administration for 90 days caused no mortality, adverse effects on general health, body and organ weights, and food intake. Furthermore, no significant variations were observed in hematological and biochemical parameters among either sex of ACP-treated and control animals. An histopathological examination of vital organs showed no significant structural changes in organs, even in high-dose ACP-treated animals. This study indicated that ACP contained the major bioactive triterpenoids of AC fruiting bodies, and its no-observed-adverse-effect level (NOAEL) was 1000 mg/kg/day, about 20 times the recommended daily intake.

Hypoglycemic Effect of Electroacupuncture Combined with Antrodia cinnamomea in Dexamethasone-Induced Insulin-Resistant Rats.

Objective: Antrodia cinnamomea (AC), a medicinal mushroom indigenous to Taiwan, exerts various pharmacologic activities. This study compared and evaluated the hypoglycemic effect of treatment with electroacupuncture (EA) combined with AC in steroid-induced insulin-resistant (SIIR) rats. Materials and Methods: Rats were divided into saline, EA, AC, AC+EA, and rosiglitazone (TZD) groups. Plasma-glucose levels were measured in serial blood samples and compared before and after treatment in each group. The levels of signaling proteins-glucose transporter 4, (GLUT4), phosphoinositide 3-kinase (PI3-K), and 5' adenosine monophosphate-activated protein kinase (AMPK)-were analyzed by Western blotting to explore their mechanisms of action. Results: The AC+EA group had reduced plasma-glucose levels at 30 and 60 minutes in SIIR rats, compared to normal rats, and this was better than the EA, AC, and TZD groups at 60 minutes. Furthermore, the signaling protein (GLUT4, PI3-K, and AMPK) levels were increased significantly. Conclusions: These findings showed improved hypoglycemic activity and insulin resistance after EA combined with AC treatment. Therefore, the combined therapy might be a more-effective method than the individual therapies that elevates the expression of the signal proteins, as observed in this study.

Extracellular Polysaccharopeptides from Fermented Turkey Tail Medicinal Mushroom, Trametes versicolor (Agaricomycetes), Mitigate Oxidative Stress, Hyperglycemia, and Hyperlipidemia in Rats with Type 2 Diabetes Mellitus.

The antihyperglycemic activity of extracellular polysaccharopeptides (ePSP) obtained from Trametes versicolor (TV) strain LH-1 has been reported to increase cellular glucose uptake in HepG2 cells in an insulin-independent manner. Evidence indicates that oxidative stress plays a pivotal role in the development of diabetic complications. We aimed to use an in vivo model to investigate the effects of TV-ePSP on oxidative stress and glucose homeostasis in type 2 diabetes mellitus (T2DM). Male Wistar rats fed with a high fat diet followed by a streptozotocin injection to induce T2DM were orally administered water or 0.1, 0.5, or 1.0 g/kg of TV-ePSP per day. After a 4-week administration of TV-ePSP, T2DM rats had attenuated elevations in blood glucose levels, areas under the curve in oral glucose tolerance tests, insulin resistance indices, and serum fructosamine and triglyceride in a dose-dependent manner (P < 0.05, one-way ANOVA). In addition, TV-ePSP significantly alleviated oxidative stress in T2DM rats, as shown by the decreased lipid peroxidation and the increased activity of superoxide dismutase in the plasma, and by the elevated glutathione levels in the plasma and erythrocytes. The antihyperglycemia and antihypertriglyceridemia activities of TV-ePSP may be associated with the improved oxidative stress, suggesting the beneficial effects of TV-ePSP in preventing the development of diabetic complications in T2DM patients.

Fruiting Bodies of Chinese Caterpillar Mushroom, Ophiocordyceps sinensis (Ascomycetes) Alleviate Diabetes-Associated Oxidative Stress.

Hyperglycemia-induced complications, the major causes of death in diabetes, are closely related to the elevated oxidative stress. Our previous study indicated that fruiting bodies of Ophiocordyceps sinensis attenuated polydipsia and hyperglycemia in diabetic rats. In this study, we further investigated whether the protective effects of O. sinensis on diabetes are associated with improved oxidative status in the circulation and target organs, the liver and kidneys. Male Wistar rats were fed with a semipurified diet supplemented with fruiting bodies (FB group, 1 g/day), carcass (CC group, 1 g/day), fruiting bodies and carcass (CF group, each 0.5 g/day), or placebo (DM and R groups) for 4 weeks (day 1 to 29). On day 15, animals were injected with nicotinamide (200 mg/kg) and streptozotocin (65 mg/kg) to induce diabetes. After the induction of diabetes, fasting blood glucose (FBG) was increased and the diabetes-increased FBG (day 15 to 26) was alleviated by the supplementation of fruiting bodies (p < 0.05, one-way ANOVA). In addition, the contents of vitamins A and C in the liver were significantly higher in the FB group, and the contents of glutathione in the liver and vitamin A and C in the kidneys were significantly higher in the FB, CC, and CF groups than in the DM group. The diabetes-increased glutathione peroxidase activity in the liver was decreased in the CF group. These results suggest that O. sinensis, especially fruiting bodies, may have antihyperglycemic activity associated with the alleviated oxidative stress in the liver and kidneys.

Electroacupuncture combined with acarbose improves insulin sensitivity via peroxisome proliferator-activated receptor γ activation and produces a stronger glucose-lowering effect than acarbose alone in a rat model of steroid-induced insulin resistance.

BACKGROUND: Previous studies have reported that electroacupuncture (EA) induces a glucose-lowering effect by improving insulin resistance (IR) and reduces plasma free fatty acid (FFA) levels in rats with steroid-induced insulin resistance (SIIR). In addition, EA can activate cholinergic nerves and stimulate endogenous opioid peptides to lower plasma glucose in streptozotocin-induced hyperglycemic rats. The aim of this study was to investigate the glucose-lowering effects of 15 Hz EA at bilateral ST36 in combination with acarbose (ACA). We hypothesized that EA combined with ACA would produce a stronger glucose-lowering effect than ACA alone. METHODS: In this study, normal Wistar rats and SIIR rats were randomly divided into two groups: ACA and ACA + EA. To explore the potential mechanisms underlying the glucose-lowering effect, plasma FFA/insulin and insulin transduction signal pathway proteins were assayed. RESULTS: Combined ACA + EA treatment had a greater glucose-lowering effect than ACA alone in normal Wistar rats (-45% ± 3% vs -19% ± 3%, p < 0.001) and SIIR model rats (-43% ± 2% vs -16% ± 6%, p < 0.001). A significant reduction in plasma FFA levels, improvement in homeostatic model assessment of IR (HOMA-IR) index (-48.9% ± 4.0%, p < 0.001) and insulin sensitivity index (102% ± 16.9%, p < 0.001), and significant increases in insulin receptor substrate 1, glucose transporter 4, and peroxisome proliferator-activated receptor γ protein expressions in skeletal muscle, were also observed in the ACA + EA group of SIIR rats. CONCLUSION: Combined EA and ACA therapy had a greater glucose-lowering effect than ACA monotherapy; this combined therapy could be more effective at improving IR in SIIR rats, which may be related to a reduction in plasma FFA levels and an elevation of insulin signaling proteins. Whether this combined therapy has an effect in type 2 diabetes mellitus (T2DM) patients still needs to be explored.

Potential activities and mechanisms of extracellular polysaccharopeptides from fermented Trametes versicolor on regulating glucose homeostasis in insulin-resistant HepG2 cells.

Polysaccharides derived from mushrooms have potential to control blood sugar, reduce insulin resistance and prevent diabetic complications. The intracellular polysaccharopeptides of Trametes versicolor (TV) have been used as immunologic and oncologic adjuvants. The aim of this study was to investigate the potential activities and mechanisms of extracellular polysaccharopeptides (ePSP) obtained from TV strain LH-1 on regulating glucose homeostasis. Human hepatoma HepG2 cells incubated with normal glucose (5.5 mM, NG model), high glucose (33 mM, HG model), or high glucose (33 mM) plus high insulin (10-7 M, HGI model) concentrations were administered with TV LH-1 ePSP (50, 100, and 1000 µg/ml) for 24 hr. Glucose uptake of HepG2 cells, determined by flow cytometry, was significantly decreased in the HG and HGI models with insulin stimulation, suggesting insulin resistance of these cells; however, ePSP reversed this decrease in a dose-dependent manner (one-way ANOVA, p<0.05). In the HG and HGI models, ePSP significantly increased glycogen content, insulin receptor substrate-2 protein and phosphorylated AMP-activated protein kinase (AMPK), as determined by western blot analysis. In addition, ePSP significantly increased glucokinase in the NG and HG models, increased membrane glucose transporter-1 and decreased glycogen synthase kinase-3ß in the HGI model, and increased glucose-6-phosphatase in the NG and HGI models (one-way ANOVA, p<0.05). In summary, TV LH-1 ePSP may elevate cellular glucose uptake to regulate glucose homeostasis via the activation of AMPK and glycogen synthesis in an insulin-independent manner. These results suggest that TV LH-1 ePSP may be a nutraceutical with anti-hyperglycemic activity.

15†Hz electroacupuncture at ST36 improves insulin sensitivity and reduces free fatty acid levels in rats with chronic dexamethasone-induced insulin resistance.

OBJECTIVE: To evaluate the effect of electroacupuncture (EA) in a rat model of chronic steroid-induced insulin resistance (SIIR). METHODS: An SIIR rat model was created using daily intraperitoneal injections of clinically relevant doses of dexamethasone (1 mg/kg) for 5 days to induce chronic insulin resistance. Thirty-six SIIR rats were randomly divided into the SIIR+EA group (n=18), which received 15 Hz EA at ST36 for 60 min, and the SIIR group (n=18), which remained untreated. Plasma glucose and free fatty acid (FFA) levels were measured in serial blood samples taken without further manipulation (n=6 per group) and during insulin challenge test (ICT, n=6 per group) and intravenous glucose tolerance test (ivGTT, n=6 per group). Insulin receptor substrate (IRS)-1 and glucose transporter (GLUT)-4 were measured using Western blotting and expressed relative to ß-actin. RESULTS: Following EA, area-under-the-curve (AUC) for glucose was reduced (7340±291 vs 10 705±1474 mg/dL/min, p=0.049) and FFA levels significantly lower at 30/60 min in the SIIR+EA versus SIIR groups. Similar effects on glucose AUC were seen during the ICT (5568±275 vs 7136±594 mg/dL/min, p<0.05) and igVTT (11 498±1398 vs 16 652±1217 mg/dL/min, p<0.01). FFA levels were lower at 30 and/or 60 min in SIIR+EA versus SIIR groups (p<0.01). Relative expression of IRS-1 and GLUT4 were significantly increased by EA (p<0.01). CONCLUSIONS: EA decreased the FFA level and increased insulin sensitivity in SIIR rats. Further clinical studies are needed to determine whether EA is an effective alternative treatment for the reduction of insulin resistance in patients requiring chronic use of dexamethasone.

Submerged-Culture Mycelia and Broth of the Maitake Medicinal Mushroom Grifola frondosa (Higher Basidiomycetes) Alleviate Type 2 Diabetes-Induced Alterations in Immunocytic Function.

Type 2 Diabetes mellitus (T2DM), a disease with impaired glucose, protein and lipid metabolism, low-grade chronic inflammation, and immune dysfunction, is a global public health crisis. We previously demonstrated that Grifola frondosa has bioactivities in improving glycemic responses in diabetic rats. Herein, we investigated the immunomodulatory effects of the submerged-culture mycelia and broth of G. frondosa on the peripheral blood cells (PBL) and splenocytes. Male Wistar rats were administered with saline (normal rats) or streptozotocin plus nicotinamide (T2DM rats) and were intragastrically administered with placebo, fermented mycelia, broth, or mycelia plus broth (1 g kg-1 day-1) for two weeks. In normal rats, ingestion of mycelia significantly decreased monocytes and ingestion of mycelia and broth significantly decreased the productions of interferon (IFN)-γ and interleukin (IL)-4 from the PBL and splenocytes. In T2DM rats, ingestion of mycelia, broth, and mycelia plus broth significantly alleviated the increases in 2 h postprandial blood glucose and the productions of IFN-γ from the T-leukocytes, IL-4, and IL-6 from the monocytes and IL-4 from the T-splenocytes, as well as significantly improved the productions of tumor-necrosis factor-α from the macrophages. In conclusion, submerged-culture mycelia and broth of G. frondosa may decrease cell-medicated immunity in normal rats and improve hyperglycemia and diabetes-induced alterations in cell-medicated and innate immunities in T2DM rats.

Polysaccharides of Trametes versicolor Improve Bone Properties in Diabetic Rats.

This study investigates the effects of Trametes versicolor (L.:Fr.) Pilát (TVP, also known as Yunzhi) on bone properties in diabetic rats. Forty-five male Wistar rats (8 weeks old) were fed either a chow diet (control) or a high-fat diet throughout the study period of 28 days. Animals in the high-fat-diet group were injected with nicotinamide and streptozotocin to induce diabetes mellitus (DM). The DM rats were divided into a group receiving distilled water (vehicle) and another group receiving TVP at 0.1 g/kg weight by gavage. Relative to the vehicle group, TVP gavage lowered postprandial blood sugar (225 ± 18 mg/dL for TVP vs 292 ± 15 mg/dL for vehicle, p < 0.001) on day 26. Compared to the vehicle group, TVP mitigated DM-induced bone deterioration as determined by increasing bone volume of proximal tibia (22.8 ± 1.4% for TVP vs 16.8 ± 1.3% for vehicle, p = 0.003), trabecular number (p = 0.011), and femoral bone strength (11% in maximal load, 22% in stiffness, 14% in modulus, p < 0.001), and by reducing loss of femoral cortical porosity by 25% (p < 0.001). Our study demonstrates the protective effect of TVP on bone properties was mediated through, in part, the improvement of hyperglycemic control in DM animals.

Intracellular signalling pathways associated with the glucose-lowering effect of ST36 electroacupuncture in streptozotocin-induced diabetic rats.

BACKGROUND AND AIM: Previous animal studies have reported a glucose-lowering effect of electroacupuncture (EA) and suggested that the mechanisms are closely related to intracellular signalling pathways. The aim of this study was to screen for potential intracellular signalling pathways that are upregulated by EA at ST36 bilaterally in rats with diabetes mellitus (DM) using microarray analysis. METHODS: Streptozotocin (STZ)-induced diabetic rats were randomly assigned to experimental (EA, n=8) or control (non-EA, n=8) groups. Plasma glucose levels were measured at baseline and after 30 and 60 min, and microarray analysis was performed on samples of gastrocnemius muscle. RESULTS: Relative to baseline values, EA significantly reduced plasma levels of glucose at 30 and 60 min. The microarray pathway analysis showed that cell adhesion molecules and type 1 DM gene sets were both upregulated in EA versus non-EA groups (p<0.05). CONCLUSIONS: Cell adhesion molecules might be related to the glucose-lowering effect induced by EA in rats with STZ-induced type 1 diabetes. Further research will be required to examine the involvement of related intracellular signalling pathways.

Biological Activities of the Polysaccharides Produced from Different Sources of Xylaria nigripes (Ascomycetes), a Chinese Medicinal Fungus.

Xylaria nigripes, a local rare medicinal fungus, has multi-antioxidant activities owing to its water extraction as shown by previous research. However, the main indicator causing the antioxidant effect was not clear, so this research focused on the antioxidant activities from different sources of X. nigripes such as fruiting body polysaccharides, mycelium intracellular polysaccharides, mycelium extracellular polysaccharides, and their deproteinization products. The mycelium intracellular polysaccharide (XnIPS-1) from X. nigripes showed the highest reducing power of antioxidant activity, since it revealed the lowest IC50 values in all the assayed methodologies. The IC50 values of chelating ferrous ion ability, ABTS radical scavenging activity, and DPPH free radical scavenging were 1412, 174.25, and 351.56 µg/mL, respectively. In addition to these results, this research also explored the mechanism between polysaccharides and antioxidants compared by FT-IR analysis. The spectrum shows that the X. nigripes polysaccharide structure changed after the proteins were removed.

The Involvement of Serotonin in the Hypoglycemic Effects Produced by Administration of the Aqueous Extract of Xylaria nigripes with Steroid-Induced Insulin-Resistant Rats.

Xylaria nigripes (XN) is a medicinal fungus with a high-economic value. The aim of this study was to explore the hypoglycemic effects and mechanisms of the XN aqueous extract in steroid-induced insulin-resistant (SIIR) rats. Significant hypoglycemic effects were observed 60 min after administration of XN aqueous extract. In normal Wistar, hypoglycemic effects were 21% (the plasma glucose level decreased from 128.6 ± 12.5 to 100.9 ± 10.7 mg/dL). In SIIR, hypoglycemic effects were 26% (the plasma glucose level decreased from 177.6 ± 12.5 to 133.3 ± 29.7 mg/dL) rats refer to their baseline. The signaling proteins for insulin-receptor substrate-1 and glucose transporter-4 increased 0.51-fold and 1.12-fold, respectively, as determined by Western blotting; the increase in the proteins was 13% and 9%, respectively, as determined by immunohistochemistry. The serotonin antagonist, α-p-chlorophenylalanine, effectively blocked the hypoglycemic effects and increased the signaling protein levels. After XN administration, none of the animals showed significant changes in plasma-free fatty acids in 60 min. In summary, the XN extract may have hypoglycemic effects in normal Wistar and SIIR rats that may have a serotonin-related hypoglycemic effect and enhance insulin sensitivity in the SIIR rats.

Effects of medium components and culture conditions on mycelial biomass and the production of bioactive ingredients in submerged culture of Xylaria nigripes (Ascomycetes), a Chinese medicinal fungus.

The optimal culture conditions were investigated to maximize the production of mycelial biomass and bioactive ingredients in submerged cultivation of Xylaria nigripes, a Chinese medicinal fungus. The one-factor-at-a-time method was used to explore the effects of medium components, including carbon, nitrogen, mineral sources, and initial pH of the medium and environmental factors, such as culture temperature and rotation speed, on mycelial growth and production of bioactive ingredients. The results indicated that the optimal culture temperature and rotation speed were 25°C and 100 rpm in a medium with 20 g fructose, 6 g yeast extract, and 2 g magnesiun sulfate heptahydrate as carbon, nitrogen, and mineral sources, respectively, in 1 L distilled water with an initial medium pH of 5.5. With optimal medium components and conditions of cultivation, the maximal production of mycelial biomass was 6.64 ± 0.88 g/L, with maximal production of bioactive ingredients such as extracellular polysaccharides (2.36 ± 0.18 mg/mL), intracellular polysaccharides (2.38 ± 0.07 mg/g), adenosine (43.27 ± 2.37 mg/g), total polyphenols (36.57 ± 1.36 mg/g), and triterpenoids (31.29 ± 1.17 mg/g) in a shake flask culture. These results suggest that different bioactive ingredients including intracellular polysaccharides, adenosine, total polyphenols and triterpenoids in mycelia and extracellular polysaccharides in broth can be obtained from one simple medium for submerged cultivation of X. nigripes.

Acupoint-specific, frequency-dependent, and improved insulin sensitivity hypoglycemic effect of electroacupuncture applied to drug-combined therapy studied by a randomized control clinical trial.

The application of electroacupuncture (EA) to specific acupoints can induce a hypoglycemic effect in streptozotocin-induced rats, normal rats, and rats with steroid-induced insulin resistance. EA combined with the oral insulin sensitizer rosiglitazone improved insulin sensitivity in rats and humans with type II diabetes mellitus (DM). There are different hypoglycemic mechanisms between Zhongwan and Zusanli acupoints by EA stimulation. On low-frequency (2 Hz) stimulation at bilateral Zusanli acupoints, serotonin was involved in the hypoglycemic effect in normal rats. Moreover, after 15 Hz EA stimulation at the bilateral Zusanli acupoints, although enhanced insulin activity mainly acts on the insulin-sensitive target organs, the muscles must be considered. In addition, 15 Hz EA stimulation at the bilateral Zusanli acupoints has the combined effect of enhancing cholinergic nerve activity and increasing nitric oxide synthase (NOS) activity to enhance insulin activity. Despite the well-documented effect of pain control by EA in many systemic diseases, there are few high-quality long-term clinical trials on the hypoglycemic effect of EA in DM. Combination treatment with EA and other medications seems to be an alternative treatment to achieve better therapeutic goals that merit future investigation.

The Fruiting Bodies, Submerged Culture Biomass, and Acidic Polysaccharide Glucuronoxylomannan of Yellow Brain Mushroom Tremella mesenterica Modulate the Immunity of Peripheral Blood Leukocytes and Splenocytes in Rats with Impaired Glucose Tolerance.

The prevalence of diabetes mellitus (DM), a chronic disease with hyperglycemia and impaired immune function, is increasing worldwide. Progression from impaired glucose tolerance (IGT) to type 2 DM has recently become a target for early intervention. The fruiting bodies (FB) and submerged culture mycelium (CM) of Tremella mesenterica, an edible and medicinal mushroom, have been demonstrated to have antihyperglycemic and immunomodulatory activities in type 1 DM rats. Herein, we investigated the effects of acidic polysaccharide glucuronoxylomannan (GX) extracted from CM on the immunocyte responses. Male Wistar rats were injected with streptozotocin (65 mg/kg) plus nicotinamide (200 mg/kg) for the induction of IGT, and gavaged daily with vehicle, FB, CM, or GX (1 g/kg/day). Rats injected with saline and gavaged vehicle were used as controls. Two weeks later, peripheral blood leukocytes (PBLs) and splenocytes were collected. Ingestion of FB, CM, and GX significantly decreased blood glucose levels in the postprandial period and in oral glucose tolerance test, and partially reversed T-splenocytic proliferation in IGT rats. CM significantly decreased T-helper lymphocytes in the PBLs and B-splenocytes. In addition, FB, CM, and GX significantly reversed the IGT-induced decreases in tumor necrosis factor-α production; GX significantly increased interleukin-6 production in T-lymphocytes in the PBLs and splenocytes; and CM and GX significantly reversed IGT-induced decrease in interferon-γ production in T-lymphocytes in the spleen. In conclusion, FB, CM, and acidic polysaccharide GX of T. mesenterica may increase T-cell immunity via the elevation of proinflammatory and T-helper cytokine production in rats with impaired glucose tolerance.

Electroacupuncture and rosiglitazone combined therapy as a means of treating insulin resistance and type 2 diabetes mellitus: a randomized controlled trial.

Aims. To evaluate the efficacy of rosiglitazone (TZD) and electroacupuncture (EA) combined therapy as a treatment for type 2 diabetes mellitus (T2DM) patients by randomized single-blind placebo controlled clinical trial. Methods. A total of 31 newly diagnostic T2DM patients, who fulfilled the study's eligibility criteria, were recruited. The individuals were randomly assigned into two groups, the control group (TZD, N = 15) and the experimental group (TZD + EA, N = 16). Changes in their plasma free fatty acid (FFA), glucose, and insulin levels, together with their homeostasis model assessment (HOMA) indices, were statistically compared before and after treatment. Hypoglycemic activity (%) was also compared between these two groups. Results. There was no significant difference in hypoglycemic activity between the TZD and TZD + EA group. The effectiveness of the combined therapy seems to derive from an improvement in insulin resistance and a significant lowering of the secreted insulin rather than the effect of TZD alone on T2DM. The combined treatment had no significant adverse effects. A lower plasma FFA concentration is likely to be the mechanism that causes this effect. Conclusion. This combined therapy seems to suppress endogenous insulin secretion by improving insulin resistance via a mechanism involving a reduction in plasma FFA. This trial is registered with ClinicalTrials.gov NCT01577095.

Aqueous extracts of Cordyceps militaris (Ascomycetes) lower the levels of plasma glucose by activating the cholinergic nerve in streptozotocin-induced diabetic rats.

In our previous research, Cordyceps militaris (CM) had a hypoglycemic effect in normal rats. In this study we wanted to elucidate whether CM also had an effect on diabetic rats. Twelve rats with streptozotocin-induced diabetes were separated randomly into 2 groups. First, aqueous extracts of CM 10 mg/kg (CM group) or saline (control group) was fed to the rats; then the plasma glucose levels were assayed. Second, the signaling proteins IRS-1 and GLUT-4 collected from the muscle were detected. Finally, another 2 groups of rats were injected with atropine 0.1 mg/kg intraperitoneally just before the CM/saline feeding, and the assays mentioned above were repeated. Blood glucose decreased 7.2% in the CM group but only 1.5% in the control group (P < 0.05). The IRS-1 signal was 2.9-fold higher than actin in the CM group but only 0.8-fold higher in the control group (P < 0.005). In GLUT-4 signal, the difference was 1.7- vs. 0.6-fold, respectively, compared with actin (P < 0.05). However, atropine injection made CM-induced hypoglycemia or elevation of IRS-1 and GLUT-4 not significant. In conclusion, CM had a hypoglycemic effect in diabetic rats and atropine blocked it. Therefore, the cholinergic activation also was considered to be involved in the hypoglycemic effect of CM in rats with streptozotocin-induced diabetes.

A Systematic Review of the Mysterious Caterpillar Fungus Ophiocordyceps sinensis in Dong-ChongXiaCao ( Dong Chóng Xià Cǎo) and Related Bioactive Ingredients.

The caterpillar fungus Ophiocordyceps sinensis (syn.Cordyceps sinensis), which was originally used in traditional Tibetan and Chinese medicine, is called either "yartsa gunbu" or "DongChongXiaCao ( Dong Chóng Xià Cǎo)" ("winter worm-summer grass"), respectively. The extremely high price of DongChongXiaCao, approximately USD $20,000 to 40,000 per kg, has led to it being regarded as "soft gold" in China. The multi-fungi hypothesis has been proposed for DongChongXiaCao; however, Hirsutella sinensis is the anamorph of O. sinensis. In Chinese, the meaning of "DongChongXiaCao" is different for O. sinensis, Cordyceps spp., and Cordyceps sp. Over 30 bioactivities, such as immunomodulatory, antitumor, anti-inflammatory, and antioxidant activities, have been reported for wild DongChongXiaCao and for the mycelia and culture supernatants of O. sinensis. These bioactivities derive from over 20 bioactive ingredients, mainly extracellular polysaccharides, intracellular polysaccharides, cordycepin, adenosine, mannitol, and sterols. Other bioactive components have been found as well, including two peptides (cordymin and myriocin), melanin, lovastatin, γ-aminobutyric acid, and cordysinins. Recently, the bioactivities of O. sinensis were described, and they include antiarteriosclerosis, antidepression, and antiosteoporosis activities, photoprotection, prevention and treatment of bowel injury, promotion of endurance capacity, and learning-memory improvement. H. sinensis has the ability to accelerate leukocyte recovery, stimulate lymphocyte proliferation, antidiabetes, and improve kidney injury. Starting January 1(st), 2013, regulation will dictate that one fungus can only have one name, which will end the system of using separate names for anamorphs. The anamorph name "H. sinensis" has changed by the International Code of Nomenclature for algae, fungi, and plants to O. sinensis.

Effects of yellow brain culinary-medicinal mushroom, Tremella mesenterica Ritz.:Fr. (higher Basidiomycetes), on immune function in normal and type 1 diabetic rats.

Diabetes mellitus (DM) is characterized by systemic low-grade inflammation and altered immunity. The fruiting bodies (FB) of Tremella mesenterica have been demonstrated to have anti-hyperglycemic and immunomodulatory activities. It is unclear whether submerged culture yeast-like cells (CC) of T. mesenterica have the same immune effects as FB. Here, we compared the immune effects of T. mesenterica FB and CC on immunocyte function. Male Wistar rats were intravenously injected with saline (normal rats) or streptozotocin (50 mg/kg, DM rats) and orally treated with placebo, FB, or CC (1 g/kg/day) for 2 weeks. Peripheral blood leukocytes and splenocytes were collected. In normal rats, FB and CC ingestion significantly decreased T-suppressor leukocyte numbers and interferon (IFN)-γ production in leukocytes (p < 0.05). In addition, CC treatment significantly decreased mitogen-stimulated tumor necrosis factor (TNF)-α and interleukin (IL)-6 production in leukocytes as well as the numbers of total and B splenocytes. In DM rats, FB significantly alleviated the diabetes-induced decreases in plasma TNF-α levels, T-helper splenocyte numbers, and IL-6 production in T leukocytes, and CC significantly attenuated the decreases in plasma TNF-α, IFN-γ, and IL-6 levels, as well as the increase in IL-6 production in T splenocytes induced by diabetes. Moreover, CC significantly decreased the numbers of T-helper leukocytes and B splenocytes as well as the production of TNF-α by splenocytes and IL-4 by leukocytes in DM rats. In conclusion, our results suggest that T. mesenterica FB and CC may decrease peripheral cell-mediated immunity in normal rats. However, in diabetic rats, FB may increase peripheral cell-mediated immunity, and CC may decrease pro-inflammatory and Th1 cytokine production.

28-day oral safety evaluation of extracellular polysaccharopeptides produced in submerged culture from the turkey tail medicinal mushroom Trametes versicolor (L.:Fr.) Pilát LH-1 in mice.

Turkey tail medicinal mushroom, Trametes versicolor (TV), is a species with a variety of pharmacological activities. Its intracellular polysaccharopeptides are widely commercialized. Recently, we found a novel TV strain LH-1 in Taiwan and demonstrated that the extracellular polysaccharopeptide (ePSP) of LH-1 obtained from submerged culture exhibits significant immunomodulatory activity. In this in vivo study, we further evaluated the safety of orally administered LH-1 ePSP using both male and female ICR mice. The LH-1 ePSP was orally administered to mice at levels of 0 (water), 100 (low dose), 500 (medium dose), or 1000 mg/kg/day (high dose) for 28 days. Clinical observations, growth, food consumption, histopathological examination, and clinical biochemical analyses revealed no adverse effects of LH-1 ePSP in mice. There were no significant differences in the results of target organ weights, hematological analyses, and urinalysis examination among groups. However, male mice that ingested high doses of LH-1 ePSP tended to have decreased lung weights and platelet numbers. In conclusion, the results of the present study suggested that oral administration of LH-1 ePSP for 28 days is accompanied by no obvious signs of toxicity. The lack of toxicity supports the potential use of LH-1 ePSP as a food or dietary supplement.