Cheol-Ho Yoon

Hexane fraction of Zingiberis Rhizoma Crudus extract inhibits the production of nitric oxide and proinflammatory cytokines in LPS-stimulated BV2 microglial cells via the NF-kappaB pathway

Excessive production of inflammatory mediators such as nitric oxide (NO), prostaglandin E(2) (PGE2), and proinflammatory cytokines, including tumor necrosis factor-alpha (TNF-alpha) and interleukin-1beta (IL-1beta) from activated microglia contributes to uncontrolled inflammation in neurodegenerative diseases. It seems possible that treatment with anti-inflammatory agents, including plants used in Oriental medicine, might delay the progression of neurodegeneration through the inhibition of microglial activation. The present study is focused on the inhibitory effect of the rhizome hexane fraction extract of Zingiber officinale Roscoe (ginger hexan extract; GHE) on the production of inflammatory mediators such as NO, PGE(2), and proinflammatory cytokines in lipopolysaccharide (LPS)-stimulated BV-2 cells, a mouse microglial cell line. GHE significantly inhibited the excessive production of NO, PGE(2), TNF-alpha, and IL-1beta in LPS-stimulated BV2 cells. In addition, GHE attenuated the mRNA expressions and protein levels of inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), and proinflammatory cytokines. The molecular mechanisms that underlie GHE-mediated attenuation are related to the inhibition of the phosphorylation of three mitogen-activated protein kinases (MAPKs), extracellular signal-regulated kinases 1 and 2 (ERK1/2), p38 MAPK, and c-Jun N-terminal kinase (JNK), and the activation of nuclear factor-kappaB (NF-kappaB). Our results indicate that GHE exhibits anti-inflammatory properties by suppressing the transcription of inflammatory mediator genes through the MAPK and NF-kappaB signaling pathways. The anti-inflammatory properties of GHE may make it useful as a therapeutic candidate for the treatment of human neurodegenerative diseases.

Anti-diabetic effect of Wen-pi-tang-Hab-Wu-ling-san extract in streptozotocin-induced diabetic rats.

Objectives: Wen-pi-tang-Hab-Wu-ling-san (WHW) is an oriental herbal prescription formulated using 14 herbs and has been used to cure chronic renal failure in Korean oriental medicine. In this study, we investigated the anti-diabetic effect of WHW in the streptozotocin-induced diabetic rats. Materials and Methods: Diabetes was induced by streptozotocin (STZ, 60 mg/kg, i.p.) in rats. WHW extract (100 mg/kg) was orally dosed once a day for four weeks. The results were compared with standard antidiabetic drug, glibenclamide (3 mg/kg, p.o). Results: Significant decrease in body weight and insulin levels and increase in blood glucose, triglycerides, urea nitrogen (BUN), and creatinine were detected in STZ-induced diabetic rats with disruption and disappearance of pancreatic and kidney cells and decrease in insulin producing beta cells. However, these diabetic changes were significantly inhibited by treatment with WHW extract. In the oral glucose tolerance test, the extract produced a significant decrease in glycemia 60 minutes after the glucose pulse. Conclusions: Based on these results, we suggest that WHW extract has favorable effects in protecting the STZ-induced hyperglycemia, renal damage, and beta-cell damage in rats.

Inhibitory activity of Drynariae rhizoma extracts on cathepsin having bone resorption activity.

Effects of traditional Korean (Hanbang) medicine, Drynariae rhizoma (DR), on the protease activity of bone loss‐initiation in rats and mice were investigated. Ethanol extracts‐DR (EE‐DR) and water extracts‐DR (WE‐DR) were identified as potent inhibitor of cathepsins K and L. The original WE‐DR inhibits cathepsins K and L with IC50 values of 3.7 µg/ml and 4.5 µg/ml, respectively. EE‐DR was more potent than that of WE‐DR, because the inhibitions of cathepsin K and L increased to 0.5 µg/ml and 0.8 µg/ml, respectively. The EE‐DR was proved to be the most potent. EE‐DR was found to be a potent inhibitor of cathepsins K with a Ki value of 5.0 µg/ml for cathepsin K. The activity was increased by 10‐fold when the assay is performed in the presence of glutathione at pH 7.0, which favors the formation of a GSH thiolate anion. Thus, it is suggested that this increase in potency is probably due to an enhanced chemical reactivity of the extract mixtures toward the thiolate of the active site of the enzyme. WE‐DR exhibited time‐dependet inhibition which allowed us to determine the association and dissociation rate constants with cathepsin K. Finally, EE‐DR inhibits bone resorption in an in vitro assay involving mouse osteoclasts and bovine bone with an IC50 value of 70 µg/ml. WE‐DR represents a new herbal formulation inhibiting cathepsin K and L activity and proteolysis of bone collagen. These results strongly suggest that DR is effective for preventing the development of bone loss induced by cathepsin K. This result also suggested that the DR is effective for bone resorptive action in bone cells.

Inhibitory effects of Bombusae concretio Salicea on neuronal secretion of Alzheimer's β-amyloid peptides, a neurodegenerative peptide

Alzheimers disease (AD) is characterized by the age-related deposition of β-amyloid (Aβ) 40/42 peptide aggregates in vulnerable brain regions. Multiple levels of evidence implicate a central role for Aβ in the pathophysiology of AD. Aβ is generated by the regulated cleavage of a = 700 amino acid Aβ precursor protein (βAPP). Full-length βAPP can undergo proteolytic cleavage either within the Aβ domain to generate secreted sβAPPα or at the N-terminal and C-terminal domain(s) of Aβ to generate amyloidogenic Aβ peptides. Several epidemiological studies have reported that estrogen replacement therapy protects against the development of AD in postmenopausal women. The aim of this study was to elucidate the antioxidant neuroprotective mechanism of Bombusae concretio Salicea (BC). BC was effective protectants against oxidative glutamate toxicity in the murine neuroblastoma cells (N2a) and human neuroblastoma cells (SK-N-MC). BC exhibited similar protective properties against oxidative glutamate toxicity and H2O2 toxicity. BC exhibited an antioxidant activity at approximately 20 μg/ml. BC of 5 μg/ml was ineffective in preventing the oxidative modification of LDL. The half-maximal effective concentration for BC was 16 μg/ml. These results suggested that BC supplementation in elderly men may be protective in the treatment of Alzheimers disease (AD). We report here that treatment with BC increases the secretion of the nonamyloidogenic APP fragment, sβAPPα and decreases the secretion of Aβ peptides from N2a cells and rat primary cerebrocortical neurons. These results raise the possibility that BC supplementation in elderly men may be protective in the treatment of AD.