Immunostimulatory Action of High-Content Active Arabinoxylan in Rice Bran.

Immunostimulatory activity comprises specific and nonspecific immune responses stimulated by internal and external factors. Arabinoxylan is well known for its immunostimulatory activity in vivo and in vitro, although the biological activities of arabinoxylan oligosaccharides depend on their structural features. In this study, we aimed to evaluate in vitro and in vivo the immunostimulatory activity of high-content active arabinoxylan (HCAA) obtained from rice bran through bioconversion by microorganisms and acid hydrolysis. Three microorganisms, Penicillium rocheforti, Aspergillus oryzae, and Pleurotus osteatus, and three different acid concentrations of hydrochloric acid (5, 10, and 20%) and acetic acid (25, 50, and 75%) were used for producing HCAA. HPLC analysis of arabinose and xylose content revealed that fermentation with P. rocheforti followed by hydrolysis with 5% hydrochloric acid was the most efficient to produce HCAA. GPC analysis of HCAA indicates that HCAA is a complex of various forms of saccharides and shows an average molecular weight of 625. Further, in vitro evaluation disclosed that exposure to HCAA (10-200 µg/mL) increased cell viability in mice splenic cells and RAW 264.7 cells. Additionally, exposure of mice to oral administration of HCAA (100 mg/kg) for 4-7 days increased lymphokine-activated killer (LAK)- and macrophage-mediated cytotoxic activity in cancer cells (YAC-1). Furthermore, in vitro exposure to HCAA and oral administrations in mice revealed increased interferon-γ (IFN-γ) and interleukin-10 (IL-10) protein expression through western blot analysis in RAW 264.7 cells and isolated splenic cells. Our results suggest that HCAA developed by bioconversion and acid hydrolysis may enhance immune responses in vivo and in vitro.

Bioconversion of Scutellaria baicalensis extract can increase recovery of auditory function in a mouse model of noise-induced hearing loss.

In noise-induced hearing loss (NIHL), noise exposure damages cochlear sensory hair cells, which lack the capacity to regenerate. Following noise insult, intense metabolic activity occurs, resulting in a cochlear free radical imbalance. Oxidative stress and antioxidant enzyme alterations, including lipoxygenase upregulation, have been linked to chronic inflammation, which contributes to hearing impairment. We previously proposed Scutellaria baicalensis (SB) extract as an alternative therapeutic for preventing NIHL and attributed its pharmacological effects to baicalein. Although baicalein was most effective, its concentration in SB extract is much lower compared to baicalin. In this study, we performed enzymatic bioconversion using an Sumizyme (SM) enzyme to increase baicalein concentration in SB extract and consequently improve its therapeutic efficacy. HPLC analysis revealed that baicalein concentration in SB extract after bioconversion (BSB) was significantly increased. Moreover, BSB-treated mice exhibited significantly improved auditory function compared with control mice and tended to have improved auditory function compared with SB-treated mice. We also demonstrated that BSB effectively stimulates hair cell regeneration compared to SB that did not achieve the same effect in a zebrafish model. Finally, when compared the abilities of SB and BSB to inhibit lipoxygenase (LOX), BSB showed a greater efficacy. Cumulatively, our data suggest that BSB exhibits improved pharmacological properties for treating NIHL compared with SB.

Enhanced antidiabetic efficacy and safety of compound K/ß-cyclodextrin inclusion complex in zebrafish.

BACKGROUND: 20(S)-Protopanaxadiol 20-O-D-glucopyranoside, also called compound K (CK), exerts antidiabetic effects that are mediated by insulin secretion through adenosine triphosphate (ATP)-sensitive potassium (KATP) channels in pancreatic ß-cells. However, the antidiabetic effects of CK may be limited because of its low bioavailability. METHODS: In this study, we aimed to enhance the antidiabetic activity and lower the toxicity of CK by including it with ß-cyclodextrin (CD) (CD-CK), and to determine whether the CD-CK compound enhanced pancreatic islet recovery, compared to CK alone, in an alloxan-induced diabetic zebrafish model. Furthermore, we confirmed the toxicity of CD-CK relative to CK alone by morphological changes, mitochondrial damage, and TdT-UTP nick end labeling (TUNEL) assays, and determined the ratio between the toxic and therapeutic dose for both compounds to verify the relative safety of CK and CD-CK. RESULTS: The CD-CK conjugate (EC50 = 2.158µM) enhanced the recovery of pancreatic islets, compared to CK alone (EC50 = 7.221µM), as assessed in alloxan-induced diabetic zebrafish larvae. In addition, CD-CK (LC50 = 20.68µM) was less toxic than CK alone (LC50 = 14.24µM). The therapeutic index of CK and CD-CK was 1.98 and 9.58, respectively. CONCLUSION: The CD-CK inclusion complex enhanced the recovery of damaged pancreatic islets in diabetic zebrafish. The CD-CK inclusion complex has potential as an effective antidiabetic efficacy with lower toxicity.

Synergistic Potentials of Coffee on Injured Pancreatic Islets and Insulin Action via KATP Channel Blocking in Zebrafish.

Pancreatic islets (PIs) are damaged under diabetic conditions, resulting in decreased PI size. This study examined the regenerative effects of coffee and its components (caffeine, CFI; trigonelline, TRG; chlorogenic acid, CGA) on zebrafish larval PIs and ß-cells damaged by administration of alloxan (AX). In addition, the influence of coffee and its active components on KATP channels was investigated using diazoxide (DZ) as a KATP channel activator. PI size and fluorescence intensity were significantly increased in the coffee-treated group relative to the no-treatment group (P < 0.0001). In addition, coffee exerted significant regenerative effects on pancreatic ß-cells (p = 0.006). Treatment with TRG and CGA rescued PI damage, and the combination of TRG/CGA had a synergistic effect. In conclusion, the results indicate that coffee has beneficial effects on AX-damaged PIs and may also be useful as a blocker of pancreatic ß-cell K(+) channels.

The efficacy of red ginseng in type 1 and type 2 diabetes in animals.

Diabetes mellitus (DM) is one of the most modern chronic metabolic diseases in the world. Moreover, DM is one of the major causes of modern neurological diseases. In the present study, the therapeutic actions of Korean red ginseng were evaluated in type 1 and type 2 diabetic mouse models using auditory electrophysiological measurement. The comprehensive results from auditory brainstem response (ABR), auditory middle latency response (AMLR), and transient evoked otoacoustic emission (TEOAE) demonstrate auditory functional damage caused by type 1 or 2 DM. Korean red ginseng improved the hearing threshold shift, delayed latencies and signal intensity decrease in type 2 diabetic mice. Type 1 diabetic mice showed a partial improvement in decreasing amplitude and signal intensity, not significantly. We suggest that the Korean red ginseng has a more potent efficacy in hearing loss in insulin resistance type 2 diabetes than in type 1 diabetes.