Byung-Keun Yang

Production of a hypoglycemic, extracellular polysaccharide from the submerged culture of the mushroom, Phellinus linteus

Mycelial growth and extracellular polysaccharide production of Phellinus linteus were optimal at pH 5 and 25 °C. Maximum biomass production (14.2 g l−1) was after 15 d of cultivation, whereas, extracellular polysaccharide was maximal (3.5 g l−1) after 21 d. The hypoglycemic effect of the polysaccharide, investigated in streptozotocin-induced diabetic rats, decreased plasma glucose, total cholesterol and triacylglycerol concentrations by 49%, 32%, and 28%, respectively, and aspartate aminotransferase activity by 20%. The results indicate the potential of this polysaccharide to prevent hyperglycemia in diabetic patients.

Hypoglycemic Effect of a Lentinus edodes Exo-polymer Producedfrom a Submerged Mycelial Culture

The hypoglycemic effect of an exo-polymer produced from a submerged mycelial culture of Lentinus edodes was investigated in streptozotocin-induced diabetic rats. The administration of the exo-polymer (200mg/kg BW) reduced the plasma glucose level by as much as 21.5%, and increased plasma insulin by 22.1% as compared to the control group. It also lowered the plasma total cholesterol and triglyceride levels by 25.1 and 44.5%, respectively. Gel chromatography of the exo-polymer revealed a single peak which is likely to have been a glycoprotein with a molecular weight of 52kDa and was found to contain 83.5% carbohydrate and 16.5% protein. The Sugar and amino acid compositions of the exo-polymer were analyzed in detail.

Hypolipidemic effect of an Exo-biopolymer produced from a submerged mycelial culture of Hericium erinaceus.

The hypolipidemic effect of an exo-biopolymer produced from a submerged mycelial culture of Hericium erinaceus was investigated in dietary-induced hyperlipidemic rats. Hypolipidemic effects were proportionally increased with the increasing concentration of the exo-biopolymer for oral administration. The exo-biopolymer, at the dose of 200 mg/kg body weight, substantially reduced the plasma total cholesterol (32.9%), LDL cholesterol (45.4%), triglyceride (34.3%), phospholipid (18.9%), atherogenic index (58.7%), and hepatic HMG-CoA reductase activity (20.2%). It increased the plasma HDL cholesterol level (31.1%) as compared to the control group. The molecular mass of this exo-biopolymer measured by HPLC was under 40 kDa. Total sugar and protein contents were 91.2 and 8.8%, respectively. The sugar and amino acid compositions of the exo-biopolymer were analyzed in detail.

Antifibrotic effect of extracellular biopolymer from submerged mycelial cultures ofCordyceps militaris on liver Fibrosis induced by Bile duct ligation and scission in rats

The antifibrotic effects of hot water extract (WEC), intracellular biopolymer (IPC) and extracellular biopolymers (EPC) from myceiial liquid culture ofCordyceps militaris on liver fibrosis were studied. Liver fibrosis was induced by a bile duct ligation and scission (BDL/S) operation, duration of 4 weeks in rats. In BDL/S rats, the levels of aspartate transaminase (AST), alanine transaminase (ALT), alkaline phosphatase (ALP), total bilirubin in serum and hydroxyproline content in liver were dramatically increased. The WEC or IPC treatment (30 mg/kg/day for 4 weeks, p.o.) in BDL/S rats reduced the serum AST, ALT and ALP levels significantly (p<0.01). The EPC treatment (30 mg/kg/day for 4 weeks, p.o.) reduced the serum ALT, AST and ALP levels significantly (p<0.01). Malondialdehyde contents in liver treated with WEC, IPC or EPC were significantly reduced (p<0.05). But Liver hydroxyproline content was decreased only in EPC treated BDL/S rats to 55% that of BDL/S control rats (p<0.01). The morphological characteristics and expression of alpha smooth muscle like actin in fibrotic liver, which appeared in BDL/S control group were improved in EPC treated fibrotic liver. These results indicate that EPC (30 mg/kg/day for 4 weeks, p.o.) has an antifibrotic effect on fibrotic rats induced by BDL/S.

Ganoderma applanatum: a promising mushroom for antitumor and immunomodulating activity.

The antitumor effect of exo‐biopolymer (EXP) produced by Ganoderma applanatum was investigated using sarcoma‐180 bearing mice. EXP, when administered (10–80 mg/kg body weight: BW) intraperitoneally, significantly inhibited the growth of solid tumor and increased the natural killer (NK) cell activity. A dose of 40 mg/kg BW was found to be highly effective, as it reduced the tumor formation by 39.7%, and increased the NK cell activity of splenocytes by 51.6% compared with the control group. The complement activity of EXP was increased in accordance with an increase in concentration. The phosphatase activity of macrophages was increased by 0.7‐fold (200 µg/mL) compared with the control group. This EXP contained 58.9% carbohydrate and 17.1% protein. The major sugar of EXP was composed of mannose and glucose, while the protein mainly consisted of serine, glycine and aspartic acid. Copyright

Isodihydrocapsiate stimulates plasma glucose uptake by activation of AMP-activated protein kinase.

AMP-activated protein kinase (AMPK) is an energy-sensing enzyme that is implicated as a key factor in controlling whole body homeostasis, including fatty acid oxidation and glucose uptake. We report that a synthetic structural isomer of dihydrocapsiate, isodihydrocapsiate (8-methylnonanoic acid 3-hydroxy-4-methoxy benzyl ester) improves type 2 diabetes by activating AMPK through the LKB1 pathway. In L6 myotube cells, phosphorylation of AMPK and acetyl-CoA carboxylase (ACC) and glucose uptake were significantly increased, whereas these effects were attenuated by an AMPK inhibitor, compound C. In addition, increased phosphorylation of AMPK and ACC by isodihydrocapsiate was significantly reduced by radicicol, an LKB1 destabilizer, suggesting that increased glucose uptake in L6 cells with isodihydrocapsiate treatment is predominantly accomplished by a LKB1-mediated AMPK activation pathway. Oral administration of isodihydrocapsiate to diabetic (db/db) mice reduced blood glucose levels by 40% after a 4-week treatment period. Our results support the development of isodihydrocapsiate as a potential therapeutic agent to target AMPK in type 2 diabetes.

Hypolipidemic effect of an exo-biopolymer produced from submerged mycelial culture of Auricularia polytricha in rats

The hypolipidemic effect of an exo-biopolymer (EBP) produced from a submerged mycelial culture of the mushroom fungus, Auricularia polytricha, was investigated in the dietary-induced hyperlipidemic rats. In a dose-dependent study, the EBP was fed at 50–100 mg kg−1 body weight and significantly decreased the concentrations of the plasma triacylglycerols, total cholesterol, and low-density lipoprotein (LDL) cholesterol. The plasma LDL cholesterol concentration was decreased up to 70%. Production of A. polytricha biomass and EBP were optimal at pH 4 with maximum growth at 20 °C and EBP production at 30 °C. Gel chromatography of the EBP revealed a single peak of a glycoprotein with a molecular size of 32 kDa. It contained 77.5% carbohydrate and 22.5% protein. The sugar and amino acid compositions of the EBP were analyzed.

Ascofuranone prevents ER stress-induced insulin resistance via activation of AMP-activated protein kinase in L6 myotube cells.

The current study presents that ascofuranone isolated from a phytopathogenic fungus, Ascochyta viciae, has antitumor activity against various transplantable tumors and a considerable hypolipidemic activity. AMP-activated protein kinase (AMPK) plays a critical role in cellular glucose and lipid homeostasis. We found that ascofuranone improves ER stress-induced insulin resistance by activating AMPK through the LKB1 pathway. In L6 myotube cells, ascofuranone treatment increased the phosphorylation of the Thr-172 residue of the AMPK alpha subunit and the Ser-79 subunit of acetyl-CoA carboxylase (ACC) and cellular glucose uptake. Ascofuranone-induced phosphorylation of AMPK and ACC was not increased in A549 cells lacking LKB1. Interestingly, ascofuranone treatment also improved insulin signaling impaired by ER stress in L6 myotube cells. These effects were all reversed by pretreatment with Compound C, an AMPK inhibitor or with adenoviral-mediated dominant-negative AMPK alpha 2. Taken together, these results indicated that ascofuranone-mediated enhancement of glucose uptake and reduction of impaired insulin sensitivity in L6 cells is predominantly accomplished by activating AMPK, thereby mediating beneficial effects in type 2 diabetes and insulin resistance.

Antidiabetic and hypolipidemic effects of Collybia confluens mycelia produced by submerged culture in streptozotocin-diabetic rats.

This investigation was undertaken to study the effects of oral administration (3 weeks) ofCollybia confluens mycelial powder (CCMP) produced by a submerged culture on plasma glucose and other biochemical parameters in streptozotocin (STZ)-induced diabetic rats. Antidiabetic and hypolipidemic effects were proportionally increased with the increasing concentration of the CCMP for oral administration. The CCMP, at the dose of 400 mg/kg BW, substantially reduced the plasma glucose level by as much as 33.1% as compared to the STZ-induced diabetic rats group. It also lowered the plasma total cholesterol, triglyceride, and low density lipoprotein (LDL) cholesterol by 22.9%, 19.9%, and 37.3%, respectively. The levels of total cholesterol and triglyceride in liver were reduced to the extent of by 13.5% and 18.8%, and the activity of alanine transaminase (ALT) and aspartate transaminase (AST) was decreased by 48.8% and 37.2%, respectively, under the influence of CCMP. The general components of CCMP were found to contain 26.18% carbohydrate, 3.67% crude ash, 4.02% crude fat, 22.55% crude protein, and 43.58% dietary fiber. The amino acid composition of the CCMP was also analyzed in detail.

Hypoglycemic Effects of Exo-biopolymers Produced by Five Different Medicinal Mushrooms in STZ-induced Diabetic Rats.

Hypoglycemic effects of exo-biopolymers (EBP) produced by submerged mycelial cultures of Coriolus versicolor, Cordyceps sinensis, Paecilomyces japonica, Armillariella mellea, and Fomes fomentarius were investigated in streptozotocin (STZ)-induced diabetic rats. The rats from each experimental group were orally administered with EBPs (100 mg/kg BW) daily for 2 weeks. Though the hypoglycemic effect was achieved in all the cases, however, C. versicolor EBP proved as the most potent one. The administration of the C. versicolor EBP substantially reduced (29.9%) the plasma glucose level as compared to the saline administered group (control). It also reduced the plasma total cholesterol (TC), triglyceride (TG), aspartate aminotransferase (AST) and, alanine aminotransferase (ALT) levels by 9.22, 23.83, 16.93, and 27.31%, respectively. The sugar and amino acid compositions of this EBP were also analyzed in detail.